Journal Article

Osteopontin promotes CCL5-mesenchymal stromal cell-mediated breast cancer metastasis

Zhiyong Mi, Syamal D. Bhattacharya, Victoria M. Kim, Hongtao Guo, Lindsay J. Talbot and Paul C. Kuo

in Carcinogenesis

Volume 32, issue 4, pages 477-487
Published in print April 2011 | ISSN: 0143-3334
Published online January 2011 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgr009
Osteopontin promotes CCL5-mesenchymal stromal cell-mediated breast cancer metastasis

More Like This

Show all results sharing this subject:

  • Clinical Cytogenetics and Molecular Genetics

GO

Show Summary Details

Preview

The interaction between cancer and its local microenvironment can determine properties of growth and metastasis. A critical component of the tumor microenvironment in this context is the cancer-associated fibroblast (CAF), which can promote tumor growth, angiogenesis and metastasis. It has been hypothesized that CAF may be derived from mesenchymal stromal cells (MSC), derived from local or distant sources. However, the signaling mechanisms by which tumors and MSCs interact to promote CAF-dependent cancer growth are largely unknown. In this study with in vitro and in vivo models using MDA-MB231 human breast cancer cells, we demonstrate that tumor-derived osteopontin (OPN) induces MSC production of CCL5; the mechanism involves OPN binding to integrin cell surface receptors and activator protein-1 c-jun homodimer transactivation. In a murine xenograft model, concomitant inoculation of MSC with MDA-MB231 cells induces: (i) significantly increased growth and metastasis of MB231 cells and (ii) increased MSC migration to metastatic sites in lung and liver; this mechanism is both OPN and CCL5 dependent. MSCs retrieved from sites of metastases exhibit OPN-dependent expression of the CAF markers, α-smooth muscle actin, tenascin-c, CXCL12 (or stromal cell-derived factor 1) and fibroblast-specific protein-1 and the matrix metalloproteinases (MMP)-2 and MMP-9. Based upon these results, we propose that tumor-derived OPN promotes tumor progression via the transformation of MSC into CAF.

Journal Article.  6266 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.