| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Tumor Biology |
Departments of Biochemistry [V. V. G., V. V. M., S. L. D., T. P. Q.], Physiology [O. V. G., V. H. H.], and Veterinary Biomedical Sciences [J. R. T., V. H. H.], University of Missouri, Columbia, Missouri 65211; Harry S. Truman Memorial Veterans Hospital [V. V. G., O. V. G., S. L. D.], Columbia, Missouri 65201; Sidney Kimmel Cancer Center and Metastat, Inc. [G. V. G.], San Diego, California 92121; and Departments of Internal Medicine and Urology [K. J. P.], University of Michigan, Ann Arbor, Michigan 48109
 |
ABSTRACT |
|---|
 Top ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
|
INTRODUCTION |
|---|
|
TopABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
Neoplastic cell heterotypic adhesion to the microvascular endothelium, resulting in tumor cell arrest in the vasculature of a target organ, is an essential early step in hematogenous cancer spread (5) . Recent observations, suggesting that only endothelium-attached malignant cells are capable of giving rise to hematogenous cancer metastases, strongly support this idea (8) . Moreover, a possible role for tumor-endothelial cell interactions in defining tissue specificity of breast and prostate cancer metastasis was recently revealed (9 , 10) .
Homotypic tumor cell adhesion (aggregation) leads to the formation of multicellular malignant cell aggregates. Because multicellular clumps could be trapped in small capillaries, the role for homotypic aggregation was postulated within the mechanical trapping theory of cancer metastasis (11) . Early pioneering works from the groups of Drs. Isaiah Fidler, Reuben Lotan, Garth Nicolson, and Avraham Raz (12, 13, 14) , as well as our previous results (6 , 15) , demonstrated that cancer cells with high metastatic potential exhibit a superior ability to form homotypic aggregates compared with their low metastatic counterparts. In several different types of cancer, the in vivo selection of tumor cells for high metastatic potential resulted in a selection of malignant cells exhibiting increased homotypic aggregation properties (6 , 12) . In addition, cancer cell lines selected in vitro for enhanced homotypic aggregation kinetics demonstrated significantly higher in vivo experimental metastatic potential than parental cells (14) . To date, metastatic cancer cell heterotypic and homotypic adhesion have been largely studied as two independent unrelated processes. Here, we demonstrate in in vitro, ex vivo, and in vivo experiments that these two processes appear to be linked together. Furthermore, it appears that in both breast and prostate cancer, heterotypic and homotypic adhesion mediated largely by similar molecular mechanisms, specifically by interactions between tumor-associated T3 glycoantigen (3) and galectin family proteins. The results presented in this article suggest that hematogenous cancer metastases could originate from multicellular aggregates formed at the sites of primary tumor cell attachment to the vascular wall. We identify interactions between T antigen and galectin-3 as one of the major pathways for mediating heterotypic and homotypic cancer cell adhesion and promoting metastatic cell clonogenic survival and growth.
|
MATERIALS AND METHODS |
|---|
|
TopABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
Cell Lines and Cultures.
The MDA-MB-435 human breast carcinoma cell line was provided by Dr. Janet Price (M. D. Anderson Cancer Center, Houston, TX). The DU-145 human prostate carcinoma cells were from American Type Culture Collection (Manassas, VA). The RPMI 1640 supplemented with L-glutamine, 10% FBS, sodium pyruvate, and nonessential amino acids was used for tumor cell lines. Immediately before adhesion experiments, cancer cells were prelabeled for 5 min with 3 µg/ml solution of acridine orange in RPMI 1640, rinsed three times with serum-free RPMI 1640, dissociated from plastic using a nonenzymatic cell dissociation reagent (Sigma), and pipetted to produce a single cell suspension. To remove any remaining cell clumps, tumor cell suspension was filtered through a 20-µm nylon mesh and adjusted to contain 5 x 104 cell/ml. A fresh neoplastic cell suspension was prepared before every injection.
Human bone marrow endothelial cell line HBMEC-60 was provided by Dr. C. Ellen van der Schoot (University of Amsterdam, Amsterdam, the Netherlands). This cell line was developed by immortalization of HBMECs originally isolated from adult human bone marrow using the amphotrophic helper-free retrovirus pLXSN16 E6/E7 (16) . The HBMEC-60 cells were shown to maintain their normal phenotype and adhesive properties, specifically the ability to bind hematopoietic progenitor cells (16) . The basal Medium 200 (Cascade Biologics, Portland, OR) supplemented with 20% FBS and low-serum growth supplement containing hydrocortisone, human fibroblast growth factor, heparin, and human epidermal growth factor was used for HBMEC-60.
In Vitro Parallel Flow Chamber Assay.
The adhesion of MDA-MB-435 and DU-145 cells to HBMECs was studied in an in vitro parallel plate laminar flow chamber as follows. HBMEC-60 was grown until 100% confluent in 35-mm tissue culture dishes coated with poly-L-lysine (10 µg/ml) overnight at 4°C. The endothelial cells were exposed to increasing wall shear stress levels in an 100-µm thick parallel plate flow chamber (Glycotech, Rockville, MD) by perfusing warm media (RPMI containing 0.75 mM Ca2+ and Mg2+ and 0.2% HSA) through a precision syringe infusion/withdrawal pump KDS210 (KD Scientific, New Hope, PA). Next, a single cell suspension of MDA-MB-435 or DU-145 cells (5 x 104 cells/ml) was perfused for a 15-min period. Tumor cell interactions with HBMECs were observed using an inverted phase contrast microscope Diavert (Leitz Wetzlar, Wetzlar, Germany) and video recorded for subsequent offline frame-by-frame analysis.
Perfused Porcine Dura Mater Model.
The dura mater corresponding to one hemisphere was collected from 9–12 month-old mature male (for prostate cancer experiments) or female (for breast cancer experiments) Yucatan miniature swine within 15–30 min after animal’s sacrifice and immediately placed on ice in a porcine Krebs solution (Krebs physiological salt supplemented with 1.0 mg/ml porcine albumin). The collected dura was dissected to allow for a flattening onto Sylgard-coated 100-mm dish and transferred onto the fluorescent video microscope stage. One of the branches of a Median Meningeal artery (typically 300–400 µm inside diameter) was cannulated using a pipette manufactured from 1-mm outer diameter borosilicate glass capillary with a 90-µm opening at the tip.
Dura mater vasculature was perfused at 30 µl/min first with porcine Krebs solution for 20 min, then with 0.3 µg/ml acridine orange solution in RPMI 1640 supplemented with 10% FBS and 1.0 mg/ml porcine albumin for an additional 40 min to visualize the perfused vascular tree. Immediately before injection, the DU-145 or MDA-MB-435 cells, prelabeled for 5 min with 3 µg/ml acridine orange solution in RPMI 1640, were dissociated from plastic and pipetted to produce a single cell suspension.
A single tumor cell suspension (5 x 104 cells/ml) was injected into the system using a chromatography injector with all Teflon-vetted parts and a 250-µl loop. Tumor cell adhesive interactions with dura microvasculature were monitored using a video microscopy system, assembled on the basis of a fixed stage fluorescent microscope Laborlux 8 (Leitz Wetzlar), equipped with a 75-W illuminator and FITC and Rhodamine filter cubes. Video images were acquired with a high sensitivity solid-state CCD video camera (COHU, Inc., San Diego, CA) and recorded at 30 frames/second.
In Vivo MDA-MB-435 Breast Carcinoma Cell Adhesion to Mouse Lung Microvasculature.
Six-week-old CB-17/ICR-SCID female mice (Harlan Sprague Dawley) were injected in the tail vein with a single cell suspension of acridine orange-labeled human carcinoma cells (2 x 106). Three h after injection, the animals were euthanized, lungs removed, and examined under a fluorescent microscope Laborlux 8 (Leitz Wetzlar), equipped with a 75-W illuminator and FITC and Rhodamine filter cubes. Video images were acquired with a high sensitivity solid-state CCD video camera (COHU, Inc.) and recorded at 30 frames/second.
Homotypic Aggregation Assay.
The effect of various concentrations (0–1.0 mM) of the lactulosyl-L-leucine and lactitol-L-leucine on DU-145 prostate carcinoma cell spontaneous aggregation was assessed using a homotypic aggregation assay as previously described (6
, 13)
.
Clonogenic Survival and Clonogenic Growth.
The MDA-MB-435 and DU-145 cells, grown until 50–60% confluent, were harvested using a nonenzymatic cell dissociation reagent as described above and plated at low density in quadruplicate (100 and 200 viable cells/well) in a 24-well culture plate without (control) or in the presence of compounds tested. Only cells with a viability of 
95% were used. Seven days later, the cells were fixed with 1% formaldehyde in PBS, stained with hematoxylin, and colonies of >10 cells were scored.
Immunofluorescence and Laser Confocal Scanning Microscopy.
The analysis of a galectin-3 cellular distribution was performed exactly as described previously (10
, 17
, 18)
. The rat anti-galectin-3 and goat Texas Red-conjugated antirat antibodies were used to visualize galectin-3 by laser scanning confocal microscopy performed on a Bio-Rad MRC 600 confocal system. Z stacks were prepared with 0.5-µm increments and analyzed in orthogonal projections (Y-Z and X-Z sections) using the MetaMorph Imaging System software (Universal Imaging, Hallis, NH). On selected orthogonal plans, to illustrate a gradient of intracellular galectin-3 expression, different colors were assigned to the areas expressing different fluorescence intensities associated with anti-galectin-3 antibody binding (purple, blue, green, yellow, and red from lowest to highest) using a Pseudocolor function of the MetaMorph Imaging System software.
The immunofluorescent analysis of the galectin-3 cell surface expression on live, nonfixed, and nonpermeabilized endothelial or neoplastic cells after a 45-min incubation at 37°C without (control) or with 1 mg/ml (final concentration) bovine fetuin or ASF or 0.5 mg/ml (final concentration) HSA or T-HSA was performed exactly as described previously (10) . The computer-assisted morphometric analysis was performed using the MetaMorph Imaging System software.
|
RESULTS |
|---|
|
TopABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
while interacting with HBMECs representing a tissue most frequently targeted by breast and prostate cancer metastasis. This is an important observation because, although both MDA-MB-435 and DU-145 metastatic human cancer cells also adhere to endothelial cells from the tissues not targeted by tumor metastasis such as HUVECs (9
, 10
, 17)
, we previously demonstrated that multiple human prostate carcinoma cell lines, including DU-145 adhere 3–5-fold greater to HBMECs than to HUVECs, aortic endothelial cells, or even HLMVECs (9)
. We next investigated whether such homotypic cancer cell aggregation occurs intravascularly.
|
. When DU-145 or MDA-MB-435 cells were injected as a single cell suspension into a porcine dura mater microvasculature perfused at the physiological rate, stably adhered carcinoma cells also frequently initiated homotypic aggregation by capturing other circulating tumor cells (Fig. 1, C and D)
. In some instances, such homotypic aggregation resulted in a formation of huge multicellular clumps within the vessels far exceeding neoplastic cells in diameter (Fig. 1E)
. These results demonstrate that homotypic cancer cell aggregation at the site of primary attachment to the endothelium occurs when breast and prostate cancer cells interact intravascularly with the endothelia of well-differentiated intact microvessels. Moreover, in perfused dura mater experiments, we often identified multiple homotypic tumor cell aggregates, formed in different microvessels, within the same observation field (Fig. 1F)
, implying that this is not a rare event but rather a common trend. Importantly, highly metastatic MDA-MB-435 breast carcinoma cells exhibited similar adhesion behavior in vivo. Injected i.v. as a single cell suspension into SCID mice, blood-borne MDA-MB-435 cells formed multiple intravascular homotypic aggregates stably adhered within mice lung microvessels (Fig. 1G)
.
Both ex vivo (Fig. 1, E and F)
and in vivo (Fig. 1G)
homotypic cancer cell aggregates reside frequently in microvessels exceeding significantly the size of the aggregates. This suggests that heterotypic adhesion to the endothelium rather than mechanical trapping is responsible for their arrest in the microcirculation. However, in some instances, it is possible that aggregates may detach and become blood borne once again, in which case one can reasonably envision their additional entrapment in small capillaries. In addition, we cannot completely rule out a multicellular neoplastic cell aggregation resulting from homotypic interactions between two or more floating tumor cells, which could lead, presumably, to mechanical lodging of such aggregates in blood microvessels as well. However, we demonstrate here (Fig. 2)
that multiple circulating cancer cells, even while in a very close proximity to each other, can pass freely through a very narrow capillary network without forming multicellular clumps and being trapped (Fig. 2A)
. These same cells do form homotypic aggregates and become permanently lodged when halted by another single cancer cell stably adhered to the microvessel wall (Fig. 2, B–E)
. Once again, in this example, stable heterotypic tumor-endothelial cell adhesion precedes homotypic aggregate formation and permanent neoplastic cell arrest in the microcirculation.
|
. In this particular experiment, prostate cancer cells avoided mechanical entrapment at the site of a microvascular spasm but became permanently attached to the vascular wall 
50 µm downstream of the constricted site in a wide part of the microvessel far exceeding the malignant cell size (Fig. 3)
. This observation highlights once again the role of heterotypic cancer-endothelial cell adhesion as an essential initial step in circulating metastatic cell permanent arrest within a microvasculature of a target organ.
|
We next investigated how these processes may be mediated at the molecular level. We previously have reported that heterotypic and homotypic cancer cell adhesion appear to be mediated at least, in part, by similar molecular mechanisms, specifically by interactions between cancer-associated carbohydrate T antigen and ß-galactoside-binding galectin family proteins (9
, 10
, 17
, 18)
. The immunodominant portion of the T antigen, a simple mucin-type core 1 disaccharide Galß1–3GalNAc, which is masked covalently or structurally on most normal cells, is exposed and immunoreactive on the outer cell surfaces of most human carcinomas and T-cell lymphomas (21
, 22)
. This carbohydrate structure plays an important role in breast and prostate cancer cell adhesion to the endothelium and homotypic aggregation (10
, 17
, 18
, 23, 24, 25, 26)
. Here, we demonstrate that lactulosyl-L-leucine (23
, 26)
, which mimic T antigen (10)
but not lactitol-L-leucine (10)
, is capable of disrupting almost entirely the DU-145 human prostate carcinoma cell homotypic aggregation (Fig. 4A)
. This result indicates that, similarly to breast cancer, prostatic malignant cell homotypic aggregation appears to be largely T antigen mediated.
|
and clonogenic growth (Fig. 4C)
. In clonogenic survival experiments, we plated breast (MDA-MB-435) and prostate (DU-145) carcinoma cells at the low density (100 or 200 cell/well in 24-well plates) in a presence of various concentration of either T antigen-mimicking lactulosyl-L-leucine (0–1.0 mM) or T antigen-masking P-30 peptide (0–50 µM). Although neither one of these two compounds causes any detectable cytotoxic or growth inhibitory effects in regular monolayer cultures, both lactulosyl-L-leucine (Fig. 4B)
and P-30 (data not shown) inhibited clonogenic survival of breast and prostate cancer cells in a dose-dependent manner. Furthermore, the surviving clones grew at a much slower rate (Fig. 4C)
, suggesting that not only clonogenic survival but also clonogenic growth of cancer cells was affected. These results indicate that in addition to promoting metastatic cell arrest in microcirculation, ß-galactoside, specifically T antigen-mediated tumor cell adhesive interactions, could be essential during early stages of metastasis formation by supporting malignant cells clonogenic survival and growth.
This idea is consistent with T antigen interacting with galectin-3. Indeed, lactulosyl-L-leucine, which blocks galectin-3 specifically by mimicking T antigen (10)
, is capable of inhibiting significantly both incidence and number of spontaneous MDA-MB-435 breast cancer metastasis in vivo (Ref. 26
and Fig. 4D
) in nude mice experiments alone without any cytotoxic drugs. The lactulosyl-L-leucine effects on cancer cell clonogenic survival and growth could be explained at least, in part, through an inhibition by this carbohydrate-amino acid conjugate of ß-galactoside-binding lectin galectin-3. Several different groups demonstrated previously the role for this intriguing multifunctional protein in prostate cancer cell adhesion to bone marrow endothelium (9
, 10
, 17)
, homotypic cell adhesion (27)
, protection from apoptosis (28
, 29) , and MDA-MB-435 breast carcinoma cell anchorage-independent clonogenic growth (30)
. Recently, we have identified galectin-3 as a binding partner for the T antigen (10
, 17)
. The lactulosyl-L-leucine interacts specifically with galectin-3 by mimicking T antigen (10)
, thus affecting the functions of this ß-galactoside-binding lectin in tumor-endothelial cell heterotypic adhesion, breast and prostate cancer cell homotypic aggregation, and metastatic cell clonogenic survival and growth. Of note, another carbohydrate-based compound also targeting specifically galectin-3, modified citrus pectin developed by the group of Dr. A. Raz, was recently shown to inhibit tumor-endothelial cell adhesion and MDA-MB-435 breast cancer metastasis in vivo as well (31)
.
Consistent with its multiple functions, galectin-3 exhibits multidirectional intracellular trafficking upon various cellular processes. Previously, we reported that during cancer cell adhesion to the endothelia, the endothelium-expressed galectin-3 is clustering toward the sites of heterotypic contacts between endothelial and breast or prostate carcinoma cells (Refs. 10
, 17
and Fig. 5, C–E, J, and L
, red arrows). Recently, Yu et al. (32)
documented the galectin-3 translocation to the perinuclear membranes in response to various apoptotic stimuli. Here, we demonstrate that in homotypic tumor cell aggregates, galectin-3 is clustering also toward the sites of cancer cell adhesion to each other (Fig. 5B, C, F, H, and K
, yellow arrows). In addition and perhaps most intriguing, within minutes of breast and prostate tumor cell interactions with endothelial monolayer, a massive nuclear trafficking of this carbohydrate binding protein occurs in cancer cells (Fig. 5, C–F, and I–L
, white arrows).
|
). We demonstrated previously that T antigen not only acts as the galectin-3 binding partner but also causes rapid galectin-3 mobilization to the endothelial cell outer surfaces (10)
. Indeed, treating endothelial cells with T antigen conjugated to T-HSA causes >3-fold increase in endothelial cell surface area positively expressing galectin-3 (Fig. 5M)
. Similarly, ASF, a glycoprotein bearing multiple T antigen moieties, but not fetuin, on which T antigen epitopes are covalently masked with sialic (neuraminic) acid, induces rapid increase in galectin-3 surface expression on breast and prostate cancer cells (Fig. 5N)
. In contrast, fetuin was reported by Zhu and Ochieng (33)
to induce rapid release of intracellular galectin-3 from tumor cells, suggesting that glycoprotein effect upon cancer cells may depend dramatically on carbohydrate moieties sialylation.
However, what factors cause galectin-3 nuclear translocation remains unknown. Interestingly, this process appears to be specific to neoplastic cell heterotypic adhesion. Galectin-3 nuclear trafficking does not occur when cancer cell interacts with each other (Fig. 5, B and H)
. Although, it is also not clear to which of the multiple functions of this intriguing carbohydrate-binding protein this phenomenon is related, it certainly reflects complex signaling pathways triggered by tumor-endothelial cell interactions, which could be critically important in determining the fate of metastatic cancer cells in circulation.
|
DISCUSSION |
|---|
|
TopABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
In addition to promoting cancer cell adhesion (10 , 17 , 18 , 26) , galectin-3 was directly implicated in malignant cell protection from apoptosis and clonogenic growth (28, 29, 30) . Thus, the galectin-3 involvement in T antigen-mediated cell-to-cell interactions provides a rationale for explaining the role for this line of intercellular communication in metastatic cell clonogenic survival and growth. Indeed, in several experimental systems, the expression of galectin-3 in cancer cells was associated with increased malignant and metastatic phenotype (37 , 38) . However, this ß-galactoside-binding lectin is not always abundantly expressed in tumor cells. For example, some prostate carcinoma cells such as LNCaP fail to express detectable galectin-3 levels (39 , 40) . This suggests that other than galectin-3 proteins, perhaps other galectin family members could potentially be involved in neoplastic cell ß-galactoside-mediated homotypic interactions.
The signaling pathways triggered by a T antigen engagement most likely depend on which glycoprotein or glycolipid this carbohydrate structure is expressed. For example, the hyaluronan receptor CD44 was identified recently as a major T antigen carrier in colon carcinoma cells (41) . The role for CD44 in tumor metastasis, specifically in homing of several different types of cancer to bone marrow as well as in mediating numerous major signaling pathways regulating cell growth, motility, and invasion, is well documented (42, 43, 44) . The function of this glycoprotein is most studied in a context of its interactions with hyaluronan, a ubiquitous component of the extracellular matrix, which also occurs transiently intracellularly. However, it would be of paramount interest to investigate if CD44-associated signaling pathways in metastatic cells could be activated by galectins through interactions with T antigen. In addition, several other mucin family members implicated in tumor cell adhesion and metastasis such as MUC1, CD146/MUC18/MCAM, or GPI-linked surface mucin CD24 could also be potentially involved in T antigen-mediated adhesion and signaling by expressing this mucin-type disaccharide (45) .
In summary, our results suggest that hematogenous cancer metastases could originate from multicellular aggregates formed at the sites of primary tumor cell attachment to the vascular wall resulting at least, in part, from ß-galactoside, specifically T antigen-mediated heterotypic and homotypic metastatic cell adhesive interactions. In addition to promoting blood-borne neoplastic cell arrest and retention in a microvasculature of a target organ, these interactions support metastatic cell clonogenic survival and growth, suggesting the involvement of major signaling pathways related to a regulation of cell growth and apoptosis. Unraveling such pathways would greatly enhance our understanding of molecular and cellular mechanisms underpinning tumor metastasis and identify new targets for developing efficient interventive cancer therapies.
|
FOOTNOTES |
|---|
1 This work was supported, in part, by NIH Grants P20 CA86290-01 (to V. V. G.), 1R43CA72284 and 1RO1CA89827-01 (to G. V. G.), T32 HL07094 (to O. V. G.), R37 HL-42528-13 and PO1 HL52490-06 (to V. H. H.), RO1 HL-36088-16 (to J. R. T.), P50 CA69568 (to K. J. P.), and DOE ER 62027 (to T. P. Q.). 
2 To whom requests for reprints should be addressed, at Department of Biochemistry, University of Missouri, 117 Schweitzer Hall, Columbia, MO 65211. Phone: (573) 814-6000, ext. 3691; Fax: (573) 814-6551; E-mail: glinskiivl{at}missouri.edu
3 The abbreviations used are: T, Thomsen-Friedenreich; HUVEC, human umbilical vein endothelial cells; HBMEC, human bone marrow endothelial cell; HLMVEC, human lung microvascular endothelial cell; FBS, fetal bovine serum; ASF, asialofetuin; T-HSA, T antigen-human serum albumin conjugate; lactulosyl-L-leucine, N-(1-deoxy-4-O-(ß-D-galactopyranos-1-yl)-D-fructofuranos-1-yl)-(S)-2-amino-4-methylpentanoic acid; CCD, charge coupled device.
Received 12/20/02. Accepted 4/23/03.
|
REFERENCES |
|---|
|
TopABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
-O). Hybridoma, 17: 165-173, 1998.[Medline]
in A431 cells. J. Cell Sci., 115: 2713-2724, 2002.This article has been cited by other articles:
|
|
 |
|
  C. Danussi, A. Coslovi, C. Campa, M. T Mucignat, P. Spessotto, F. Uggeri, S. Paoletti, and A. Colombatti A newly generated functional antibody identifies Tn antigen as a novel determinant in the cancer cell-lymphatic endothelium interaction Glycobiology, October 1, 2009; 19(10): 1056 - 1067. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Hu, L. Sun, C. Guo, Q. Liu, Z. Zhou, L. Peng, J. Pan, L. Yu, J. Lou, Z. Yang, et al. Tumor Cell-Microenvironment Interaction Models Coupled with Clinical Validation Reveal CCL2 and SNCG as Two Predictors of Colorectal Cancer Hepatic Metastasis Clin. Cancer Res., September 1, 2009; 15(17): 5485 - 5493. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. IURISCI, A. CUMASHI, A. A. SHERMAN, Y. E. TSVETKOV, N. TINARI, E. PICCOLO, M. D'EGIDIO, V. ADAMO, C. NATOLI, G. A. RABINOVICH, et al. Synthetic Inhibitors of Galectin-1 and -3 Selectively Modulate Homotypic Cell Aggregation and Tumor Cell Apoptosis Anticancer Res, January 1, 2009; 29(1): 403 - 410. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. R Barthel, J. D Gavino, G. K Wiese, J. M Jaynes, J. Siddiqui, and C. J Dimitroff Analysis of glycosyltransferase expression in metastatic prostate cancer cells capable of rolling activity on microvascular endothelial (E)-selectin Glycobiology, October 1, 2008; 18(10): 806 - 817. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. V. Mossine, P. Chopra, and T. P. Mawhinney Interaction of Tomato Lycopene and Ketosamine against Rat Prostate Tumorigenesis Cancer Res., June 1, 2008; 68(11): 4384 - 4391. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. Stowell, C. M. Arthur, P. Mehta, K. A. Slanina, O. Blixt, H. Leffler, D. F. Smith, and R. D. Cummings Galectin-1, -2, and -3 Exhibit Differential Recognition of Sialylated Glycans and Blood Group Antigens J. Biol. Chem., April 11, 2008; 283(15): 10109 - 10123. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Shen, J. J. Rahn, J. Zhang, N. Gunasekera, X. Sun, A. R.E. Shaw, M. J. Hendzel, P. Hoffman, A. Bernier, and J. C. Hugh MUC1 Initiates Src-CrkL-Rac1/Cdc42-Mediated Actin Cytoskeletal Protrusive Motility after Ligating Intercellular Adhesion Molecule-1 Mol. Cancer Res., April 1, 2008; 6(4): 555 - 567. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. L. Thijssen, S. Hulsmans, and A. W. Griffioen The Galectin Profile of the Endothelium: Altered Expression and Localization in Activated and Tumor Endothelial Cells Am. J. Pathol., February 1, 2008; 172(2): 545 - 553. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. L. J. L. Thijssen, F. Poirier, L. G. Baum, and A. W. Griffioen Galectins in the tumor endothelium: opportunities for combined cancer therapy Blood, October 15, 2007; 110(8): 2819 - 2827. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.-G. Yu, N. Andrews, Q. Zhao, D. McKean, J. F. Williams, L. J. Connor, O. V. Gerasimenko, J. Hilkens, J. Hirabayashi, K. Kasai, et al. Galectin-3 Interaction with Thomsen-Friedenreich Disaccharide on Cancer-associated MUC1 Causes Increased Cancer Cell Endothelial Adhesion J. Biol. Chem., January 5, 2007; 282(1): 773 - 781. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Schluter, P. Gassmann, A. Enns, T. Korb, A. Hemping-Bovenkerk, J. Holzen, and J. Haier Organ-Specific Metastatic Tumor Cell Adhesion and Extravasation of Colon Carcinoma Cells with Different Metastatic Potential Am. J. Pathol., September 1, 2006; 169(3): 1064 - 1073. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Mina-Osorio, L. H. Shapiro, and E. Ortega CD13 in cell adhesion: aminopeptidase N (CD13) mediates homotypic aggregation of monocytic cells J. Leukoc. Biol., April 1, 2006; 79(4): 719 - 730. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. A. Rabinovich, A. Cumashi, G. A. Bianco, D. Ciavardelli, I. Iurisci, M. D'Egidio, E. Piccolo, N. Tinari, N. Nifantiev, and S. Iacobelli Synthetic lactulose amines: novel class of anticancer agents that induce tumor-cell apoptosis and inhibit galectin-mediated homotypic cell aggregation and endothelial cell morphogenesis Glycobiology, March 1, 2006; 16(3): 210 - 220. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Dimitroff Sharing the Same Vascular Addressins for Osteotropic Behavior of Hematopoietic Progenitor Cells and Cancer IBMS BoneKEy, October 1, 2005; 2(10): 16 - 19. [Full Text] [PDF]
|
|
|
|
|
|
F. Santos-Silva, A. Fonseca, T. Caffrey, F. Carvalho, P. Mesquita, C. Reis, R. Almeida, L. David, and M. A. Hollingsworth Thomsen-Friedenreich antigen expression in gastric carcinomas is associated with MUC1 mucin VNTR polymorphism Glycobiology, May 1, 2005; 15(5): 511 - 517. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Berezovskaya, A. D. Schimmer, A. B. Glinskii, C. Pinilla, R. M. Hoffman, J. C. Reed, and G. V. Glinsky Increased Expression of Apoptosis Inhibitor Protein XIAP Contributes to Anoikis Resistance of Circulating Human Prostate Cancer Metastasis Precursor Cells Cancer Res., March 15, 2005; 65(6): 2378 - 2386. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Zou, V. V. Glinsky, L. A. Landon, L. Matthews, and S. L. Deutscher Peptides specific to the galectin-3 carbohydrate recognition domain inhibit metastasis-associated cancer cell adhesion Carcinogenesis, February 1, 2005; 26(2): 309 - 318. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Dimitroff, M. Lechpammer, D. Long-Woodward, and J. L. Kutok Rolling of Human Bone-Metastatic Prostate Tumor Cells on Human Bone Marrow Endothelium under Shear Flow Is Mediated by E-Selectin Cancer Res., August 1, 2004; 64(15): 5261 - 5269. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. I. Romanov, T. Whyard, H. L. Adler, W. C. Waltzer, and S. Zucker Prostate Cancer Cell Adhesion to Bone Marrow Endothelium: The Role of Prostate-Specific Antigen Cancer Res., March 15, 2004; 64(6): 2083 - 2089. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. V. Glinskii, J. R. Turk, K. J. Pienta, V. H. Huxley, and V. V. Glinsky Evidence of porcine and human endothelium activation by cancer-associated carbohydrates expressed on glycoproteins and tumour cells J. Physiol., January 1, 2004; 554(1): 89 - 99. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
