Role of the matricelular protein SPARC in breast tumor grouth and metastatic disemination.

BENEDETTI, LORENA; SALVATIERRA, EDGARDO; GÜTTLEIN, LEANDRO; FRESNO, CRISTOBAL; FERNÁNDEZ, ELMER ANDRÉS; MANSILLA, SABRINA; GOTTIFREDI, VANESA; LLERA, ANDREA SABINA; PODHAJCER, OSVALDO LUIS

Illinois

Congreso; American Association for Cancer Research Anual Meeting 2012; 2012

American Association for Cancer Research

Breast cancer is the elading cause of death on women worldwide. Whereas surgical resection and adjuvant therapy can cure well-confined primary tumors, metastatic disease is largely incurable because of its systemic nature and resistance of disseminated tumor cells to existing therapeutic agents. SPARC is a matricellular protein whose normal expression is associated with remodelling tissues. In this context SPARC was described as involved in cell cycle, proliferation, invasion, migration, angiogenesis and apoptosis. Expression array technology among other approaches identified SPARC as marker of poor prognosis, very often associated with most agressive tumors in the vast majority of human cancer types. However, there is confusing data regarding the role of this protein expressed by epithelial or stromal cells during the development and progression of breast tumors. In the present work, we used the murine metastatic breast cancer model, 4T1, to achieve a better understanding of the role of SPARC expressed by epithelial cells during breast cancer progression. We showed for the first time that SPARC expressed by epithelial tumor cells favors both, breast tumor growth and metastatic behaviour through different mechanisms. Moreover, using microarray technology, we were able to identify a set of genes regulated by SPARC expression that are related to the metastatic phenotype and that can be early deteded during tumor grouth.