| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Tumor Biology |
The First Department of Internal Medicine [T. F., Y. T., K. F., S. M., K. S., S. Y., S. E.] and Department of Immunology [U. Y.], University of Occupational and Environmental Health, Japan, School of Medicine, Kitakyushu 807-8555, Japan, and Department of Cancer Biology and Molecular Immunology, Faculty of Pharmaceutical Science, University of Tokyo, Tokyo 113-0033, Japan [T. I.]
For cancer metastasis, tumor cells present in the circulation must first adhere to the endothelium. Integrins lymphocyte function-associated antigen (LFA) 1 and very late antigen 4 play a central role in leukocyte adhesion to the endothelium and subsequent migration into tissues. The majority of tumor cells derived from solid cancers including colorectal cancer do not express suitable adhesion receptors, LFA-1 and very late antigen 4. We investigated the mechanisms of adhesion and transendothelial migration of cancer cells using colorectal carcinoma cell lines. Our results showed the following novel features of CD44 on the cells: (a) colon cancer cells express high levels of CD44; (b) stimulation of cancer cells by CD44 cross-linking or fragmented hyaluronan markedly induces the expression of LFA-1s, some of which reveal an activation epitope on the cells; (c) CD44 cross-linking induces F-actin polymerization in the cell cortex; (d) fragmented hyaluronan induces up-regulation of the activation epitope of LFA-1, which is mediated through protein kinase C; (e) stimulation of CD44 augments the LFA-1-mediated adhesion of cancer cells to endothelial cells and intercellular adhesion molecule 1-transfected cells and facilitates transendothelial migration; (f) stimulation of CD44 also induces expression of the hepatocyte growth factor (HGF) receptor c-Met on cancer cells; and (g) HGF further amplifies the LFA-1-mediated adhesion of cells prestimulated by CD44-derived signaling. Our results indicated that stimulation by CD44 induces "outside-in signaling," which consists of a direct pathway via CD44 and an alternate pathway through the induction of c-Met expression via HGF. Such stimuli augment the expression and trigger the function of integrins via "inside-out signaling" in colon cancer cells, which leads to amplification of integrin-mediated adhesion to the vessel wall and subsequent transendothelial migration.
This article has been cited by other articles:
|
|
 |
|
  Q. Zhao, X. Guo, G. B. Nash, P. C. Stone, J. Hilkens, J. M. Rhodes, and L.-G. Yu Circulating Galectin-3 Promotes Metastasis by Modifying MUC1 Localization on Cancer Cell Surface Cancer Res., September 1, 2009; 69(17): 6799 - 6806. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Vachon, R. Martin, V. Kwok, V. Cherepanov, C.-W. Chow, C. M. Doerschuk, J. Plumb, S. Grinstein, and G. P. Downey CD44-mediated phagocytosis induces inside-out activation of complement receptor-3 in murine macrophages Blood, December 15, 2007; 110(13): 4492 - 4502. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. R. Rodrigues, J. A. Teixeira, F. L. Schmitt, M. Paulsson, and H. Lindmark-Mansson The Role of Osteopontin in Tumor Progression and Metastasis in Breast Cancer Cancer Epidemiol. Biomarkers Prev., June 1, 2007; 16(6): 1087 - 1097. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Nataatmadja, J. West, and M. West Overexpression of Transforming Growth Factor-{beta} Is Associated With Increased Hyaluronan Content and Impairment of Repair in Marfan Syndrome Aortic Aneurysm Circulation, July 4, 2006; 114(1_suppl): I-371 - I-377. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Burdick, J. T. Chu, S. Godar, and R. Sackstein HCELL Is the Major E- and L-selectin Ligand Expressed on LS174T Colon Carcinoma Cells J. Biol. Chem., May 19, 2006; 281(20): 13899 - 13905. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. N. Sugahara, T. Hirata, H. Hayasaka, R. Stern, T. Murai, and M. Miyasaka Tumor Cells Enhance Their Own CD44 Cleavage and Motility by Generating Hyaluronan Fragments J. Biol. Chem., March 3, 2006; 281(9): 5861 - 5868. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Karadag, N. S. Fedarko, and L. W. Fisher Dentin Matrix Protein 1 Enhances Invasion Potential of Colon Cancer Cells by Bridging Matrix Metalloproteinase-9 to Integrins and CD44 Cancer Res., December 15, 2005; 65(24): 11545 - 11552. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. I. Khan, S. M. Kerfoot, B. Heit, L. Liu, G. Andonegui, B. Ruffell, P. Johnson, and P. Kubes Role of CD44 and Hyaluronan in Neutrophil Recruitment J. Immunol., December 15, 2004; 173(12): 7594 - 7601. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Annabi, S. Thibeault, R. Moumdjian, and R. Beliveau Hyaluronan Cell Surface Binding Is Induced by Type I Collagen and Regulated by Caveolae in Glioma Cells J. Biol. Chem., May 21, 2004; 279(21): 21888 - 21896. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Takeda, H. Terasawa, M. Sakakura, Y. Yamaguchi, M. Kajiwara, H. Kawashima, M. Miyasaka, and I. Shimada Hyaluronan Recognition Mode of CD44 Revealed by Cross-saturation and Chemical Shift Perturbation Experiments J. Biol. Chem., October 31, 2003; 278(44): 43550 - 43555. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. N. Sugahara, T. Murai, H. Nishinakamura, H. Kawashima, H. Saya, and M. Miyasaka Hyaluronan Oligosaccharides Induce CD44 Cleavage and Promote Cell Migration in CD44-expressing Tumor Cells J. Biol. Chem., August 22, 2003; 278(34): 32259 - 32265. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Lauer-Fields, N. B. Malkar, G. Richet, K. Drauz, and G. B. Fields Melanoma Cell CD44 Interaction with the alpha 1(IV)1263-1277 Region from Basement Membrane Collagen Is Modulated by Ligand Glycosylation J. Biol. Chem., April 11, 2003; 278(16): 14321 - 14330. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Orian-Rousseau, L. Chen, J. P. Sleeman, P. Herrlich, and H. Ponta CD44 is required for two consecutive steps in HGF/c-Met signaling Genes & Dev., December 1, 2002; 16(23): 3074 - 3086. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Rescher, A. Danielczyk, A. Markoff, and V. Gerke Functional Activation of the Formyl Peptide Receptor by a New Endogenous Ligand in Human Lung A549 Cells J. Immunol., August 1, 2002; 169(3): 1500 - 1504. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Suzuki, H. Kobayashi, M. Fujie, T. Nishida, M. Takigawa, N. Kanayama, and T. Terao Kunitz-type Protease Inhibitor Bikunin Disrupts Phorbol Ester-induced Oligomerization of CD44 Variant Isoforms Containing Epitope v9 and Subsequently Suppresses Expression of Urokinase-type Plasminogen Activator in Human Chondrosarcoma Cells J. Biol. Chem., March 1, 2002; 277(10): 8022 - 8032. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Yasuda, Y. Tanaka, K. Fujii, and K. Yasumoto CD44 stimulation down-regulates Fas expression and Fas-mediated apoptosis of lung cancer cells Int. Immunol., October 1, 2001; 13(10): 1309 - 1319. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Medico, A. Gentile, C. L. Celso, T. A. Williams, G. Gambarotta, L. Trusolino, and P. M. Comoglio Osteopontin Is an Autocrine Mediator of Hepatocyte Growth Factor-induced Invasive Growth Cancer Res., August 1, 2001; 61(15): 5861 - 5868. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Thomas and P.M. Speight Cell Adhesion Molecules and Oral Cancer Critical Reviews in Oral Biology & Medicine, January 1, 2001; 12(6): 479 - 498. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Mummert, M. Mohamadzadeh, D. I. Mummert, N. Mizumoto, and A. Takashima Development of a Peptide Inhibitor of Hyaluronan-Mediated Leukocyte Trafficking J. Exp. Med., September 18, 2000; 192(6): 769 - 780. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. S. Sherman, T. A. Rizvi, S. Karyala, and N. Ratner Cd44 Enhances Neuregulin Signaling by Schwann Cells J. Cell Biol., September 4, 2000; 150(5): 1071 - 1084. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Li, N. Wong, M. D. Jabali, and P. Johnson CD44-initiated Cell Spreading Induces Pyk2 Phosphorylation, Is Mediated by Src Family Kinases, and Is Negatively Regulated by CD45 J. Biol. Chem., July 27, 2001; 276(31): 28767 - 28773. [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 |
