| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Immunology |
Department of Pathology, Tumor Immunology, University of Regensburg, 93042 Regensburg, Germany
ABSTRACT
Natural killer (NK) cells provide effective antitumoral activity in the blood stream of mice, leading to reduced metastasis. There are, however, tumor cells that metastasize despite the presence of an intact NK system. The capability of tumor cells to induce platelet aggregation, on the other hand, correlates with their enhanced metastatic potential. A counteractive role of platelets for the NK function in metastasis has never been conceived. Here we demonstrate for the first time that platelets directly protect tumor cells from NK lysis in vitro as well as in vivo. Using three different tumor cell lines in a mouse model of experimental metastasis, tumor seeding in the target organs was reduced when the host was platelet depleted, but only if the tumor cells were NK sensitive. Aggregation of platelets around tumor cells also inhibited in vitro NK tumorilytic activity. This protection of tumor cells by platelets was mouse strain independent and was equally observed with platelets from ß2-microglobulin-deficient mice, excluding a NK inhibitory function of MHC class I on platelets. Thus, even if tumor cells are NK susceptible and cytotoxic NK cells threaten their survival in the blood, platelets are capable of protecting them from cytolysis, thereby promoting metastasis. Surface shielding by platelet aggregates seems to be the main mechanism of this protection.
This article has been cited by other articles:
|
|
 |
|
  H. Laubli, K.-S. Spanaus, and L. Borsig Selectin-mediated activation of endothelial cells induces expression of CCL5 and promotes metastasis through recruitment of monocytes Blood, November 12, 2009; 114(20): 4583 - 4591. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. May, I. Hagedorn, I. Pleines, M. Bender, T. Vogtle, J. Eble, M. Elvers, and B. Nieswandt CLEC-2 is an essential platelet-activating receptor in hemostasis and thrombosis Blood, October 15, 2009; 114(16): 3464 - 3472. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-G. Kopp, T. Placke, and H. R. Salih Platelet-Derived Transforming Growth Factor-{beta} Down-Regulates NKG2D Thereby Inhibiting Natural Killer Cell Antitumor Reactivity Cancer Res., October 1, 2009; 69(19): 7775 - 7783. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. YOSHIKAWA, M. KUNITOMO, S. KAGOTA, K. SHINOZUKA, and K. NAKAMURA Inhibitory Effect of Cordycepin on Hematogenic Metastasis of B16-F1 Mouse Melanoma Cells Accelerated by Adenosine-5'-diphosphate Anticancer Res, October 1, 2009; 29(10): 3857 - 3860. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Ho-Tin-Noe, T. Goerge, and D. D. Wagner Platelets: Guardians of Tumor Vasculature Cancer Res., July 15, 2009; 69(14): 5623 - 5626. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. N. Thomas, R. L. Schnaar, and K. Konstantopoulos Podocalyxin-like protein is an E-/L-selectin ligand on colon carcinoma cells: comparative biochemical properties of selectin ligands in host and tumor cells Am J Physiol Cell Physiol, March 1, 2009; 296(3): C505 - C513. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-G. Kopp, T. Placke, B. J Schmiedel, L. Kanz, M. Krusch, and H. R Salih NK Cell Anti-Tumor Reactivity Is Impaired by Platelet-Derived TGF-B through NKG2D Downregulation Blood (ASH Annual Meeting Abstracts), November 16, 2008; 112(11): 2859 - 2859. [Abstract]
|
|
|
|
 |
|
 N. Li Platelet-lymphocyte cross-talk J. Leukoc. Biol., May 1, 2008; 83(5): 1069 - 1078. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. S. Alves, M. M. Burdick, S. N. Thomas, P. Pawar, and K. Konstantopoulos The dual role of CD44 as a functional P-selectin ligand and fibrin receptor in colon carcinoma cell adhesion Am J Physiol Cell Physiol, April 1, 2008; 294(4): C907 - C916. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Palumbo, K. E. Talmage, J. V. Massari, C. M. La Jeunesse, M. J. Flick, K. W. Kombrinck, Z. Hu, K. A. Barney, and J. L. Degen Tumor cell-associated tissue factor and circulating hemostatic factors cooperate to increase metastatic potential through natural killer cell-dependent and-independent mechanisms Blood, July 1, 2007; 110(1): 133 - 141. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Jain, M. Zuka, J. Liu, S. Russell, J. Dent, J. A. Guerrero, J. Forsyth, B. Maruszak, T. K. Gartner, B. Felding-Habermann, et al. Platelet glycoprotein Ib{alpha} supports experimental lung metastasis PNAS, May 22, 2007; 104(21): 9024 - 9028. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Borsig, L. Wang, M. C. M. Cavalcante, L. Cardilo-Reis, P. L. Ferreira, P. A. S. Mourao, J. D. Esko, and M. S. G. Pavao Selectin Blocking Activity of a Fucosylated Chondroitin Sulfate Glycosaminoglycan from Sea Cucumber: EFFECT ON TUMOR METASTASIS AND NEUTROPHIL RECRUITMENT J. Biol. Chem., May 18, 2007; 282(20): 14984 - 14991. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. L. Napier, Z. R. Healy, R. L. Schnaar, and K. Konstantopoulos Selectin Ligand Expression Regulates the Initial Vascular Interactions of Colon Carcinoma Cells: THE ROLES OF CD44V AND ALTERNATIVE SIALOFUCOSYLATED SELECTIN LIGANDS J. Biol. Chem., February 9, 2007; 282(6): 3433 - 3441. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Chiodoni, M. Iezzi, C. Guiducci, S. Sangaletti, I. Alessandrini, C. Ratti, F. Tiboni, P. Musiani, D. N. Granger, and M. P. Colombo Triggering CD40 on endothelial cells contributes to tumor growth J. Exp. Med., October 30, 2006; 203(11): 2441 - 2450. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Brown, M. M. Fuster, R. Li, N. Varki, C. A. Glass, and J. D. Esko A disaccharide-based inhibitor of glycosylation attenuates metastatic tumor cell dissemination. Clin. Cancer Res., May 1, 2006; 12(9): 2894 - 2901. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Laubli, J. L. Stevenson, A. Varki, N. M. Varki, and L. Borsig L-Selectin Facilitation of Metastasis Involves Temporal Induction of Fut7-Dependent Ligands at Sites of Tumor Cell Arrest Cancer Res., February 1, 2006; 66(3): 1536 - 1542. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Weiler A platelet cloak for tumor cells Blood, January 1, 2005; 105(1): 5 - 6. [Full Text] [PDF]
|
|
|
|
|
|
J. S. Palumbo, K. E. Talmage, J. V. Massari, C. M. La Jeunesse, M. J. Flick, K. W. Kombrinck, M. Jirouskova, and J. L. Degen Platelets and fibrin(ogen) increase metastatic potential by impeding natural killer cell-mediated elimination of tumor cells Blood, January 1, 2005; 105(1): 178 - 185. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Im, W. Fu, H. Wang, S. K. Bhatia, D. A. Hammer, M. A. Kowalska, and R. J. Muschel Coagulation Facilitates Tumor Cell Spreading in the Pulmonary Vasculature during Early Metastatic Colony Formation Cancer Res., December 1, 2004; 64(23): 8613 - 8619. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Hoeben, B. Landuyt, M. S. Highley, H. Wildiers, A. T. Van Oosterom, and E. A. De Bruijn Vascular Endothelial Growth Factor and Angiogenesis Pharmacol. Rev., December 1, 2004; 56(4): 549 - 580. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Alifano, G. Benedetti, and R. Trisolini Can Low-Molecular-Weight Heparin Improve the Outcome of Patients With Operable Non-Small Cell Lung Cancer?: An Urgent Call for Research Chest, August 1, 2004; 126(2): 601 - 607. [Full Text] [PDF]
|
|
|
|
|
|
M. M. Burdick and K. Konstantopoulos Platelet-induced enhancement of LS174T colon carcinoma and THP-1 monocytoid cell adhesion to vascular endothelium under flow Am J Physiol Cell Physiol, August 1, 2004; 287(2): C539 - C547. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Wei, G. Tai, Y. Gao, N. Li, B. Huang, Y. Zhou, S. Hao, and X. Zeng Modified Heparin Inhibits P-selectin-mediated Cell Adhesion of Human Colon Carcinoma Cells to Immobilized Platelets under Dynamic Flow Conditions J. Biol. Chem., July 9, 2004; 279(28): 29202 - 29210. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Ludwig, B. Boehme, M. Podda, R. Henschler, E. Jager, C. Tandi, W.-H. Boehncke, T. M. Zollner, R. Kaufmann, and J. Gille Endothelial P-Selectin as a Target of Heparin Action in Experimental Melanoma Lung Metastasis Cancer Res., April 15, 2004; 64(8): 2743 - 2750. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Sayeh, K. Sterling, E. Speck, J. Freedman, and J. W. Semple IgG antiplatelet immunity is dependent on an early innate natural killer cell-derived interferon-{gamma} response that is regulated by CD8+ T cells Blood, April 1, 2004; 103(7): 2705 - 2709. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Borsig Selectins Facilitate Carcinoma Metastasis and Heparin Can Prevent Them Physiology, February 1, 2004; 19(1): 16 - 21. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Fuster, J. R. Brown, L. Wang, and J. D. Esko A Disaccharide Precursor of Sialyl Lewis X Inhibits Metastatic Potential of Tumor Cells Cancer Res., June 1, 2003; 63(11): 2775 - 2781. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Palumbo, J. M. Potter, L. S. Kaplan, K. Talmage, D. G. Jackson, and J. L. Degen Spontaneous Hematogenous and Lymphatic Metastasis, but not Primary Tumor Growth or Angiogenesis, Is Diminished in Fibrinogen-deficient Mice Cancer Res., December 1, 2002; 62(23): 6966 - 6972. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Borsig, R. Wong, R. O. Hynes, N. M. Varki, and A. Varki Synergistic effects of L- and P-selectin in facilitating tumor metastasis can involve non-mucin ligands and implicate leukocytes as enhancers of metastasis PNAS, February 19, 2002; 99(4): 2193 - 2198. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Borsig, R. Wong, J. Feramisco, D. R. Nadeau, N. M. Varki, and A. Varki Heparin and cancer revisited: Mechanistic connections involving platelets, P-selectin, carcinoma mucins, and tumor metastasis PNAS, March 13, 2001; 98(6): 3352 - 3357. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. J. T. McCarty, S. A. Mousa, P. F. Bray, and K. Konstantopoulos Immobilized platelets support human colon carcinoma cell tethering, rolling, and firm adhesion under dynamic flow conditions Blood, September 1, 2000; 96(5): 1789 - 1797. [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 |
