This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services 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 Yamada, K. M. Articles by Akiyama, S. K. Search for Related Content PubMed PubMed Citation Articles by Yamada, K. M. Articles by Akiyama, S. K.

Monoclonal Antibody and Synthetic Peptide Inhibitors of Human Tumor Cell Migration¹

Membrane Biochemistry Section, Laboratory of Molecular Biology, National Cancer Institute [K. M. Y., D. W. K., S. S. Y., W.-T. C., S. K. A.]; Hematology Service, Clinical Center [H. G.], National Institutes of Health, Bethesda, Maryland 20892, and Department of Anatomy and Cell Biology and Lombardi Cancer Research Center, Georgetown University School of Medicine, Washington, DC 20007 [W.-T. C.]; and Departments of Biochemistry and Oncology, Howard University Cancer Center, Howard University College of Medicine, Washington, DC 20060 [S. K. A.]

The processes of migration and invasion by human tumor cells are likely to involve specific cell surface receptors, such as receptors for the extracellular matrix molecules fibronectin, laminin, and collagen. We have examined the roles of several of these receptors using a set of monoclonal antibodies directed against the ß₁ integrin family, as well as a series of synthetic peptides reported to inhibit various interactions of each of these proteins with the cell surface. The most general inhibitor of tumor cell migration was found to be the anti-ß₁ monoclonal antibody 13, which inhibited the migration of human HT-1080 fibrosarcoma cells, 5637 bladder carcinoma cells, VA13 viral transformants, and HCT 116 colon carcinoma cells when fibronectin was the migration substrate. Moreover, this antibody was particularly effective in blocking cell migration on laminin, as well as migration within 3-dimensional collagen gels. It also inhibited in vitro invasiveness in a reconstituted basement membrane invasion assay (Matrigel assay) at concentrations as low as 1 µg/ml. Integrins of the ß₁ class thus appear to play a central role in several types of migration by a variety of human tumor cell lines. Anti-₅ fibronectin receptor monoclonal antibody 16 also significantly inhibited migration on fibronectin, but not on other substrates, in 3 of the 4 cell lines. Conversely, anti-₂ monoclonal antibody F17 strikingly inhibited migration in 3-dimensional collagen gels, but not on other substrates, implicating the ₂ß₁ integrin system in migration of tumor cells within collagenous matrices. A series of synthetic peptides previously reported to inhibit interactions of normal cells with fibronectin, laminin, and collagen were also tested as inhibitors of tumor cell migration. Peptides containing the Arg-Gly-Asp adhesive recognition signal were partially inhibitory, but with occasional exceptions, most other peptides had no effects on migration. Our results indicate the central importance of several specific ß₁ integrins in human tumor cell migration and show the effectiveness of monoclonal antibody treatment in blocking this process in vitro.

¹ Portions of this study were supported by National Institutes of Health grants CA 45515 and CA 14818 to S. K. A. and HL 33711 to W.-T. C. and a Howard University Faculty Research Support grant to S. K. A.

² To whom requests for reprints should be addressed, at the National Cancer Institute, Building 36, Room 1D32, NIH, Bethesda, MD 20892.

Received 10/ 2/89. Revised 3/27/90.

This article has been cited by other articles:

				N. Vainionpaa, Y. Kikkawa, K. Lounatmaa, J. H. Miner, P. Rousselle, and I. Virtanen Laminin-10 and Lutheran blood group glycoproteins in adhesion of human endothelial cells Am J Physiol Cell Physiol, March 1, 2006; 290(3): C764 - C775. [Abstract] [Full Text] [PDF]

				R. Montesano, P. Soulie, J. A. Eble, and F. Carrozzino Tumour necrosis factor {alpha} confers an invasive, transformed phenotype on mammary epithelial cells J. Cell Sci., August 1, 2005; 118(15): 3487 - 3500. [Abstract] [Full Text] [PDF]

				S. Filenius, T. Tervo, and I. Virtanen Production of Fibronectin and Tenascin Isoforms and Their Role in the Adhesion of Human Immortalized Corneal Epithelial Cells Invest. Ophthalmol. Vis. Sci., August 1, 2003; 44(8): 3317 - 3325. [Abstract] [Full Text] [PDF]

				S. Yamada, H. Fujiwara, T. Honda, T. Higuchi, T. Nakayama, T. Inoue, M. Maeda, and S. Fujii Human granulosa cells express integrin {alpha}2 and collagen type IV: possible involvement of collagen type IV in granulosa cell luteinization Mol. Hum. Reprod., July 1, 1999; 5(7): 607 - 617. [Abstract] [Full Text] [PDF]

				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]

				H Stanton, J Gavrilovic, S. Atkinson, M. d'Ortho, K. Yamada, L Zardi, and G Murphy The activation of ProMMP-2 (gelatinase A) by HT1080 fibrosarcoma cells is promoted by culture on a fibronectin substrate and is concomitant with an increase in processing of MT1-MMP (MMP-14) to a 45 kDa form J. Cell Sci., January 9, 1998; 111(18): 2789 - 2798. [Abstract] [PDF]

				R.-i. Manabe, N. Oh-e, T. Maeda, T. Fukuda, and K. Sekiguchi Modulation of Cell-adhesive Activity of Fibronectin by the Alternatively Spliced EDA Segment J. Cell Biol., October 6, 1997; 139(1): 295 - 307. [Abstract] [Full Text] [PDF]

				W.-c. Ho, C. Heinemann, D. Hangan, S. Uniyal, V. L. Morris, and B. M.C. Chan Modulation of In Vivo Migratory Function of alpha 2beta 1 Integrin in Mouse Liver Mol. Biol. Cell, October 1, 1997; 8(10): 1863 - 1875. [Abstract] [Full Text]

				E. I. Deryugina and M. A. Bourdon Tenascin mediates human glioma cell migration and modulates cell migration on fibronectin J. Cell Sci., March 1, 1996; 109(3): 643 - 652. [Abstract] [PDF]

				B. Chan, N Matsuura, Y Takada, B. Zetter, and M. Hemler In vitro and in vivo consequences of VLA-2 expression on rhabdomyosarcoma cells Science, March 29, 1991; 251(5001): 1600 - 1602. [Abstract] [PDF]