help button home button Am J Pathol Angiogenesis Meeting
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Material
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Said, N.
Right arrow Articles by Motamed, K.
Right arrow Search for Related Content
PubMed
Right arrow Articles by Said, N.
Right arrow Articles by Motamed, K.
(American Journal of Pathology. 2007;170:1054-1063.)
© 2007 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2007.060903

Secreted Protein Acidic and Rich in Cysteine (SPARC) Inhibits Integrin-Mediated Adhesion and Growth Factor-Dependent Survival Signaling in Ovarian Cancer

Neveen Said*, Ida Najwer* and Kouros Motamed*{dagger}

From the Vascular Biology Center* and Department of Pathology,{dagger} Medical College of Georgia, Augusta, Georgia

The matricellular glycoprotein SPARC (secreted protein acidic and rich in cysteine) has been accorded major roles in regulation of cell adhesion and proliferation, as well as tumorigenesis and metastasis. We have recently reported that in addition to its potent antiproliferative and proapoptotic functions, SPARC also abrogates ovarian carcinoma cell adhesion, a key step in peritoneal implantation. However, the underlying molecular mechanism through which SPARC ameliorates peritoneal ovarian carcinomatosis seems to be multifaceted and has yet to be delineated. Herein, we show that SPARC significantly inhibited integrin-mediated ovarian cancer cell adhesion to extracellular matrix proteins, as well as to peritoneal mesothelial cells. This counteradhesive effect of SPARC was shown to be mediated in part through significant attenuation of cell surface expression and clustering of {alpha}v-integrin subunit, {alpha}vß3- and {alpha}vß5-heterodimers, and ß1-subunit, albeit to a lesser extent, in ovarian cancer cells. Moreover, SPARC significantly suppressed both anchorage-dependent and -independent activation of AKT and mitogen-acti-vated protein kinase survival signaling pathways in ovarian cancer cells in response to serum and epidermal growth factor stimulation. In summary, we have identified a novel role of SPARC as a negative regulator of both integrin-mediated adhesion and growth factor-stimulated survival signaling pathways in ovarian cancer.




This article has been cited by other articles:


Home page
 Mol Cancer ResHome page
N. Said, M. J. Socha, J. J. Olearczyk, A. A. Elmarakby, J. D. Imig, and K. Motamed
Normalization of the Ovarian Cancer Microenvironment by SPARC
Mol. Cancer Res., October 1, 2007; 5(10): 1015 - 1030.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2007 by the American Society for Investigative Pathology.