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J. Biol. Chem., Vol. 279, Issue 17, 17731-17737, April 23, 2004

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_v-Integrin Utilization in Human -Cell Adhesion, Spreading, and Motility^*

Thomas Kaido, Brandon Perez, Mayra Yebra, Jesse Hill, Vincenzo Cirulli, Alberto Hayek, and Anthony M. Montgomery

From the Islet Research Laboratory at The Whittier Institute for Diabetes, Department of Pediatrics, The University of California at San Diego, La Jolla, California 92037

The role of individual integrins in human -cell development and function is largely unknown. This study describes the contribution of _v-integrins to human -cell adhesion, spreading, and motility. Developmental differences in _v-integrin utilization are addressed by comparing the responses of adult and fetal -cells, and vitronectin is used as a substrate based on its unique pattern of expression in the developing pancreas. Fetal and adult -cells attached equally to vitronectin and integrin _v5 was found to support the adhesion of both mature and immature -cell populations. Fetal -cells were also observed to spread and migrate on vitronectin, and integrin _v1 was found to be essential for these responses. In contrast to their fetal counterparts, adult -cells failed to either spread or migrate and this deficit was associated with a marked down-regulation of _v1 expression in adult islet preparations. The integrin _v3 was not found to support significant -cell attachment or migration. Based on our findings, we conclude that integrins _v5 and _v1 are important mediators of human -cell adhesion and motility, respectively. By supporting fetal -cell migration, _v1 could play an important role in early motile processes required for islet neogenesis.

Received for publication, August 1, 2003 , and in revised form, January 9, 2004.

^* This work was supported by Juvenile Diabetes Research Foundation Grant JDRFI Award 1-20001-793 (to A. M. M.) and by the Larry L. Hillblom Foundation. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: The Islet Research Laboratory at The Whittier Inst. for Diabetes, Dept. of Pediatrics, The University of California at San Diego, 9894 Genesee Ave. La Jolla, CA 92037. Tel.: 858-550-2909; Fax: 858-558-3495; E-mail: ammontgo{at}ucsd.edu.

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