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Volume 272, Number 33, Issue of August 15, 1997 pp. 20835-20843
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

Chromogranin A Fragments Modulate Cell Adhesion
IDENTIFICATION AND CHARACTERIZATION OF A PRO-ADHESIVE DOMAIN

(Received for publication, October 29, 1996, and in revised form, May 21, 1997)

Anna Gasparri , Alessandro Sidoli , Lincidio Perez Sanchez , Renato Longhi ^§ , Antonio G. Siccardi ^¶ , Pier Carlo Marchisio and Angelo Corti

From the Department of Biological and Technological Research, San Raffaele Scientific Institute, 20132 Milan, ^§ Consiglio Nazionale delle Ricerche, 20131 Milan, ^¶ Department of Biology and Genetics for Medical Sciences, University of Milan, 20131 Milan, and the  Department of Biomedical Sciences and Human Oncology, University of Torino School of Medicine, 10126 Torino, Italy

Although several functions have been suggested for chromogranin A, a glycoprotein secreted by many neuroendocrine cells, the physiological role of this protein and of its proteolytic fragments has not been established. We have found that mixtures of chromogranin A fragments can inhibit fibroblast adhesion. The anti-adhesive activity was converted into pro-adhesive activity by limited trypsin treatment. Pro-adhesive effects were observed also with recombinant N-terminal fragments corresponding to residues 1-78 and 1-115 and with a synthetic peptide encompassing the residues 7-57. These fragments induced adhesion and spreading of fibroblasts on plates coated with collagen I or IV, laminin, fetal calf serum (FCS) but not on bovine serum albumin. The long incubation time required for adhesion assays (4 h) and the FCS requirements for optimal adhesion suggest that the adhesive activity is likely indirect and requires other proteins present in the FCS or made by the cells.

These findings suggest that chromogranin A and its fragments could play a role in the regulation of cell adhesion. Since chromogranin A is concentrated and stored within granules and rapidly released by neuroendocrine cells and neurons after an appropriate stimulus, this protein could be important for the local control of cell adhesion by stimulated cells.

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