Functional Interactions Between Laminin-10, alphaV beta3 Integrin and Matrix Metalloproteinase-9 in Promoting Breast Cancer Metastasis to Bone
Abstract
The purpose of this work was to investigate the functional interact ions between laminin (LN)-10, integrin alphav beta3 and matrix metalloproteinase (MMP)-9 in the metastasis of breast tumors to bone. Whilst both alphav beta3 and MMP-9 have been implicated in bone metastasis, their relationship to LN-10 in this process remains largely unknown. We hypothesized that LN- 10 contributes to breast cancer metastasis through direct interaction with alphav beta3 and modulation of MMP-9 expression. Using a novel immunohistochemistry protocol, we found that aggressive 4T1.2 primary tumors and lung and bone metastases express high levels of LN-10 (alpha5 chain) but not LN-1 or LN-5. LN-10 is a potent adhesive substrate for mammary carcinoma cell lines irrespective of their metastatic potential but selectively promotes alphav beta3-dependent migration and MMP-9 expression of bone metastatic lines. Migration on LN-10 is inhibited by blocking antibodies directed against beta3 integrin, specific alphavbeta3-binding LN-10 peptides or by down-regulation of MMP-9 expression in bone metastatic cells. The anti-metastatic potential of LN peptides is currently being tested in vivo. These findings suggest that LN-10 may have prognostic and/or therapeutic value for the treatment of metastasis breast tumors.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2005
- Accession Number
- ADA446940
Entities
People
- Normand Pouliot
Organizations
- University of Melbourne