Osteopontin-induced, integrin-dependent migration of human mammary epithelial cells involves activation of the hepatocyte growth factor receptor (Met)
Osteopontin (OPN) is a secreted glycophosphoprotein which induces migration of mammary carcinoma cells, and has been implicated in the malignancy of breast carcinoma. Hepatocyte growth factor (HGF) induces cell migration of several mammary epithelial cell (MEC) lines, via activation of its cognate r...
Saved in:
Published in | Journal of cellular biochemistry Vol. 78; no. 3; pp. 465 - 475 |
---|---|
Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
New York
John Wiley & Sons, Inc
01.09.2000
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | Osteopontin (OPN) is a secreted glycophosphoprotein which induces migration of mammary carcinoma cells, and has been implicated in the malignancy of breast carcinoma. Hepatocyte growth factor (HGF) induces cell migration of several mammary epithelial cell (MEC) lines, via activation of its cognate receptor (Met). This study examines the mechanism of OPN‐induced MEC migration, in terms of the cell surface integrins involved and induction of the HGF/Met pathway. Three different MEC cell lines were used, representing different stages of tumor progression: 21PT, non‐tumorigenic; 21NT, tumorigenic; non‐metastatic; and MDA‐MB‐435, tumorigenic, highly metastatic. Human recombinant OPN was found to induce the migration of all three lines. OPN‐induced migration of 21PT and 21NT cells was αvβ5 and β1‐integrin dependent, and αvβ3‐independent, while that of MDA‐MB‐435 cells was αvβ3‐dependent. HGF also induced migration of all three cell lines, and a synergistic response was seen to HGF and OPN together. The increased migration response to OPN was found to be associated with an initial increase in Met kinase activity (within 30 min), followed by an increase in Met mRNA and protein expression. OPN‐induced cell migration is thus mediated by different cell surface integrins in MEC lines representing different stages of progression, and involves activation of the HGF receptor, Met. J. Cell. Biochem. 78:465–475, 2000. © 2000 Wiley‐Liss, Inc. |
---|---|
Bibliography: | istex:A8734F507EF6B57E1D08979A2BDDF60BF7CCFDB1 ark:/67375/WNG-VK83MMGQ-Z The content of this article does not necessarily reflect the position or policy of the U.S. government, and no official endorsement should be inferred. Canadian Breast Cancer Research Initiative - No. 8426 U.S. Army Breast Cancer Research Program - No. DAMD17-96-1-6075 U.S. Army Medical Research and Materials Command - No. DAMD17-96-1-6251 ArticleID:JCB11 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0730-2312 1097-4644 |
DOI: | 10.1002/1097-4644(20000901)78:3<465::AID-JCB11>3.0.CO;2-C |