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Research Article Free access | 10.1172/JCI119298

Insulin-like growth factor receptor cooperates with integrin alpha v beta 5 to promote tumor cell dissemination in vivo.

P C Brooks, R L Klemke, S Schon, J M Lewis, M A Schwartz, and D A Cheresh

Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA. pcbrooks@riscsm.scripps.edu

Find articles by Brooks, P. in: JCI | PubMed | Google Scholar

Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA. pcbrooks@riscsm.scripps.edu

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Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA. pcbrooks@riscsm.scripps.edu

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Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA. pcbrooks@riscsm.scripps.edu

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Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA. pcbrooks@riscsm.scripps.edu

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Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA. pcbrooks@riscsm.scripps.edu

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First published March 15, 1997 - More info

Published in Volume 99, Issue 6 on March 15, 1997
J Clin Invest. 1997;99(6):1390–1398. https://doi.org/10.1172/JCI119298.
© 1997 The American Society for Clinical Investigation
First published March 15, 1997 - Version history
Abstract

Tumor cell interactions with adhesion proteins and growth factors likely contribute to the metastatic cascade. Evidence is provided that insulin or insulin-like growth factor-mediated signals cooperate with the commonly expressed integrin alpha v beta 5 to promote spontaneous pulmonary metastasis of multiple tumor cell types in both the chick embryo and severe combined immune deficiency mouse/human chimeric models. Expression of alpha v beta 5 in tumor cells promoted their adhesion to vitronectin in vitro. However, cell motility required cytokine stimulation, which caused redistribution of alpha-actinin to membrane-adhesive sites containing alpha v beta 5. Significantly, ligation of alpha v beta 5 and cytokine receptors were both required for spontaneous pulmonary metastasis of multiple tumor types even though it was not necessary for primary tumor growth. Thus, tumor cell metastasis can be regulated by a functional cooperation between cytokine signaling events and the adhesion receptor alpha v beta 5 in a manner independent of tumor cell growth. These findings provide evidence that integrin ligation, in conjunction with cytokine activation, plays an important role in the dissemination of malignant tumor cells.

Version history
  • Version 1 (March 15, 1997): No description

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