Details

Autor(en) / Beteiligte

• Felding-Habermann, Brunhilde
• O'Toole, Timothy E.
• Smith, Jeffrey W.
• Fransvea, Emilia
• Ruggeri, Zaverio M.
• Ginsberg, Mark H.
• Hughes, Paul E.
• Pampori, Nisar
• Shattil, Sanford J.
• Saven, Alan
• Mueller, Barbara M.

Titel

Integrin Activation Controls Metastasis in Human Breast Cancer

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2001-02, Vol.98 (4), p.1853-1858

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2001

Quelle

MEDLINE

Beschreibungen/Notizen

• Metastasis is the primary cause of death in human breast cancer. Metastasis to bone, lungs, liver, and brain involves dissemination of breast cancer cells via the bloodstream and requires adhesion within the vasculature. Blood cell adhesion within the vasculature depends on integrins, a family of transmembrane adhesion receptors, and is regulated by integrin activation. Here we show that integrin αvβ3 supports breast cancer cell attachment under blood flow conditions in an activation-dependent manner. Integrin αvβ3 was found in two distinct functional states in human breast cancer cells. The activated, but not the nonactivated, state supported tumor cell arrest during blood flow through interaction with platelets. Importantly, activated αvβ3 was expressed by freshly isolated metastatic human breast cancer cells and variants of the MDA-MB 435 human breast cancer cell line, derived from mammary fat pad tumors or distant metastases in severe combined immunodeficient mice. Expression of constitutively activated mutant α vβ 3D723R, but not α vβ 3WTin MDA-MB 435 cells strongly promoted metastasis in the mouse model. Thus breast cancer cells can exhibit a platelet-interactive and metastatic phenotype that is controlled by the activation of integrin αvβ3. Consequently, alterations within tumors that lead to the aberrant control of integrin activation are expected to adversely affect the course of human breast cancer.