HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science 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 ISI Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Glover, S. Articles by Benya, R. V. Search for Related Content PubMed PubMed Citation Articles by Glover, S. Articles by Benya, R. V.

HORMONES AND SIGNALING

Transient upregulation of GRP and its receptor critically regulate colon cancer cell motility during remodeling

¹Department of Medicine, University of Illinois at Chicago and Chicago Veterans Administration Medical Center (West Side Division), Chicago, Illinois; ²Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, Florida; and ³Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, Illinois

Submitted 9 March 2004 ; accepted in final form 30 November 2004

Gastrin-releasing peptide (GRP) is typically viewed as a growth factor in cancer. However, we have suggested that in colon cancer, GRP acts primarily as a morphogen when it and its receptor (GRP-R) are aberrantly upregulated. As such, GRP/GRP-R act(s) primarily to modulate processes contributing to the assumption or maintenance of tumor differentiation. One of the most important such processes is the ability of tumor cells to achieve directed motility in the context of tissue remodeling. Yet the cellular conditions affecting GRP/GRP-R expression, and the biochemical pathways involved in mediating its morphogenic properties, remain to be established. To study this, we evaluated the human colon cancer cell lines Caco-2 and HT-29 cells. We found that confluent cells do not express GRP/GRP-R. In contrast, disaggreation and plating at subconfluent densities results in rapid GRP/GRP-R upregulation followed by their progressive decrease as confluence is achieved. GRP/GRP-R coexpression correlated with that of focal adhesion kinase (FAK) phosphorylation of Tyr³⁹⁷, Tyr⁴⁰⁷, Tyr⁸⁶¹, and Tyr⁹²⁵ but not Tyr⁵⁷⁶ or Tyr⁵⁷⁷. To more specifically evaluate the kinetics of GRP/GRP-R upregulation, we wounded confluent cell monolayers. At t = 0 h GRP/GRP-R were not expressed, yet cells immediately began migrating into the gap created by the wound. GRP/GRP-R were first detected at 2 h, and maximal levels were observed at 6 h postwounding. The GRP-specific antagonist [D-Phe⁶]-labeled bombesin methyl ester had no effect on cell motility before GRP-R expression. In contrast, this agent increasingly attenuated cell motility with increasing GRP-R expression such that from t = 6 h onward no further cell migration into the gap was observed. Overall, these findings indicate the existence of GRP-independent and -dependent phases of tumor cell remodeling with the latter mediating colon cancer cell motility during remodeling via FAK.

bombesin; morphogen; motogen

This article has been cited by other articles:

				L. Taglia, D. Matusiak, K. A. Matkowskyj, and R. V. Benya Gastrin-releasing peptide mediates its morphogenic properties in human colon cancer by upregulating intracellular adhesion protein-1 (ICAM-1) via focal adhesion kinase Am J Physiol Gastrointest Liver Physiol, January 1, 2007; 292(1): G182 - G190. [Abstract] [Full Text] [PDF]