This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hangan, D. Articles by Chan, B. M. C. Search for Related Content PubMed PubMed Citation Articles by Hangan, D. Articles by Chan, B. M. C.

An Epitope on VLA-6 (6ß1) Integrin Involved in Migration but not Adhesion Is Required for Extravasation of Murine Melanoma B16F1 Cells in Liver¹

Departments of Microbiology and Immunology [D. H., V. L. M., L. B., C. v. B., S. U., B. M. C. C.], Medical Biophysics [V. L. M.], and Oncology [V. L. M.], and Transplantation and Immunobiology Group [D. H., L. B., C. v. B., S. U., B. M. C. C.], John P. Robarts Research Institute, University of Western Ontario, London, Ontario, N6A 5K8 Canada

VLA-6 (6ß1) integrin represents the major receptor for interaction with laminin substrate. It has been proposed that VLA-6 mediates tumor cell adhesion to the endothelium during extravasation. We have further explored this possibility using mouse melanoma B16F1 cells, which express VLA-6 as the principal laminin receptor, and two VLA-6 monoclonal antibodies (mAbs), MA6 and GoH3. Adhesion is a prerequisite of cell movement on matrix proteins. Thus, GoH3, which inhibited VLA-6-mediated adhesion, blocked cell movement on laminin. The recently prepared 6 integrin-specific mAb MA6 bound to an epitope in close proximity to GoH3, but it had no effect on VLA-6-mediated cell adhesion. We report here that although MA6 did not affect adhesion, it blocked mouse melanoma B16F1 cell movement on laminin to the same extent as GoH3. Results therefore demonstrate an active role of VLA-6 in providing cell movement as well as the initial adhesive event on laminin. In addition, mAb MA6 had no effect on the induction of tyrosine phosphorylation of focal adhesion kinase upon adhesion of B16F1 cells to laminin. Therefore, inhibition of cell movement by MA6 involved mechanism(s) other than an interference of VLA-6 signaling events leading to phosphorylation of focal adhesion kinase. The epitopes of GoH3 and MA6 may represent spatially and temporally related sites on VLA-6 that are involved during cell movement, or, alternatively, MA6 may inhibit the interaction of VLA-6 with associated cell surface molecules required for cell movement. In vivo videomicroscopy experiments also revealed that an inhibition of VLA-6 migratory function by MA6 resulted in a reduction in the ability of B16F1 to extravasate during hematogenous metastasis in the liver.

¹ Supported by the Medical Research Council of Canada (B. M. C. C.), the Natural Sciences and Engineering Research Council of Canada (B. M. C. C.), and the Cancer Research Society and Academic Development Fund of the University of Western Ontario (V. L. M. and B. M. C. C.).

² To whom requests for reprints should be addressed, at Transplantation and Immunobiology Group. John P. Robarts Research Institute, University of Western Ontario, 100 Perth Drive, London, Ontario, Canada N6A 5K8. Phone: (519) 663-3300, extension 4206; Fax: (519) 663-3789; E-mail: bosco@immune.rri.uwo.ca.

Received 1/27/97. Accepted 7/ 1/97.

This article has been cited by other articles:

				E. Delamarre, S. Taboubi, S. Mathieu, C. Berenguer, V. Rigot, J.-C. Lissitzky, D. Figarella-Branger, L. Ouafik, and J. Luis Expression of Integrin {alpha}6{beta}1 Enhances Tumorigenesis in Glioma Cells Am. J. Pathol., August 1, 2009; 175(2): 844 - 855. [Abstract] [Full Text] [PDF]

				M. O. Ports, R. B. Nagle, G. D. Pond, and A. E. Cress Extracellular Engagement of {alpha}6 Integrin Inhibited Urokinase-Type Plasminogen Activator-Mediated Cleavage and Delayed Human Prostate Bone Metastasis Cancer Res., June 15, 2009; 69(12): 5007 - 5014. [Abstract] [Full Text] [PDF]

				S. Silletti, M. Yebra, B. Perez, V. Cirulli, M. McMahon, and A. M. P. Montgomery Extracellular Signal-regulated Kinase (ERK)-dependent Gene Expression Contributes to L1 Cell Adhesion Molecule-dependent Motility and Invasion J. Biol. Chem., July 9, 2004; 279(28): 28880 - 28888. [Abstract] [Full Text] [PDF]

				Q. D. Wu, J. H. Wang, C. Condron, D. Bouchier-Hayes, and H. P. Redmond Human neutrophils facilitate tumor cell transendothelial migration Am J Physiol Cell Physiol, April 1, 2001; 280(4): C814 - C822. [Abstract] [Full Text] [PDF]

				C. Ballestrem, B. Wehrle-Haller, B. Hinz, and B. A. Imhof Actin-dependent Lamellipodia Formation and Microtubule-dependent Tail Retraction Control-directed Cell Migration Mol. Biol. Cell, September 1, 2000; 11(9): 2999 - 3012. [Abstract] [Full Text]

				D Nath, P. Slocombe, A Webster, P. Stephens, A. Docherty, and G Murphy Meltrin gamma(ADAM-9) mediates cellular adhesion through alpha(6)beta(1 )integrin, leading to a marked induction of fibroblast cell motility J. Cell Sci., January 6, 2000; 113(12): 2319 - 2328. [Abstract] [PDF]

				B. L. Ziober, Y. Q. Chen, D. M. Ramos, N. Waleh, and R. H. Kramer Expression of the {{alpha}}7{beta}1 Laminin Receptor Suppresses Melanoma Growth and Metastatic Potential Cell Growth Differ., July 1, 1999; 10(7): 479 - 490. [Abstract] [Full Text]

				A. Lochter, M. Navre, Z. Werb, and M. J. Bissell alpha 1 and alpha 2 Integrins Mediate Invasive Activity of Mouse Mammary Carcinoma Cells through Regulation of Stromelysin-1 Expression Mol. Biol. Cell, February 1, 1999; 10(2): 271 - 282. [Abstract] [Full Text]

				R. L. Yauch, F. Berditchevski, M. B. Harler, J. Reichner, and M. E. Hemler Highly Stoichiometric, Stable, and Specific Association of Integrin alpha 3beta 1 with CD151 Provides a Major Link to Phosphatidylinositol 4-Kinase, and May Regulate Cell Migration Mol. Biol. Cell, October 1, 1998; 9(10): 2751 - 2765. [Abstract] [Full Text]

				S. Z. Domanico, A. J. Pelletier, W. L. Havran, and V. Quaranta Integrin alpha 6Abeta 1 Induces CD81-dependent Cell Motility without Engaging the Extracellular Matrix Migration Substrate Mol. Biol. Cell, November 1, 1997; 8(11): 2253 - 2265. [Abstract] [Full Text]

				M. Sixt, R. Hallmann, O. Wendler, K. Scharffetter-Kochanek, and L. M. Sorokin Cell Adhesion and Migration Properties of beta 2-Integrin Negative Polymorphonuclear Granulocytes on Defined Extracellular Matrix Molecules. RELEVANCE FOR LEUKOCYTE EXTRAVASATION J. Biol. Chem., May 25, 2001; 276(22): 18878 - 18887. [Abstract] [Full Text] [PDF]