CD151 Synergy With ErbB Receptors During Human Breast Cancer
Abstract
Recent studies have suggested that a3pl and a6P4 integrins, receptors for extracellular matrix laminin, synergize with oncogenic ErbB receptor kinases to promote mammary tumor malignancy and drug resistance. Given the strong physical link of these receptors with CD151, a 30 kDa cell surface protein and member of the tetraspanin family, we proposed to study if CD151 is a viable target for human breast cancer treatment. Our project focused on those tumor cells overexpressing EGFR and ErbB2, two oncogenic members of ErbB receptor family. We hypothesized that CD151 acts together with EGFR or ErbB2 to affect tumor cell sensitivity to currently available biological therapeutic agents, including clinically used kinase inhibitors. Using culture breast cancer cell lines and xenograft animal models we examined CD151 effects on mammary tumor cell motility, , malignancy and proliferation. Our dab demonstrated that ablating CD151 markedly inhibited tumor cell migration and invasion on laminin substrate but had minimal effect on cell proliferation. Also, removal of CD151 enhanced mammary tumor sensitivity to treatment with ErbB inhibitor Herceptin and Lapatinib. Furthermore, our results showed that CD151 affects ErbB receptor signaling in a laminin-binding integrin-dependent manner. Collectively, our studies support a critical role for CD151 in ErBBZpositive breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2008
- Accession Number
- ADA501759
Entities
People
- Xiuwei Yang
Organizations
- Dana–Farber Cancer Institute