Seminar

Unravelling breast to lung metastasis suppression functions

Roger Gomis, PhD

Our current understanding of the biology of breast cancer metastasis is a major barrier to identify novel therapies and improve existing therapies for the treatment and prevention of this disease. Metastasis occurs when tumor cells acquire the ability to escape their original location and invade healthy tissue and organs elsewhere in the body. This complex cellular process, virtually unique to cancer, raises fundamental questions about the role that certain genes play in determining how and why tumor cells break free and, once mobile, how they decide where to attack. Our work focuses on breast cancer metastatic suppressor genes and their functions in the metastatic process. For this, we are using the MDA-MB-231 breast cancer cell line model and their derivatives #4175 and #1833, which have a strong metastatic capacity to lung and bone. We used these subpopulations to functionally validate a particular metastasis suppressor whose loss of expression in ER- breast cancer cells confers a selective advantage for the colonization of lung. Tumor cells under certain conditions cannot grow or survive in the absence of a supportive microenvironment. Indeed, the microenvironment may even drive tumor and metastasis development by selecting for highly invasive and resistant cancer cell phenotypes and systemically fostering the mobilization of marrow-derived progenitor cell. In particular, loss of expression of our gene of interest is selected in the primary tumor. Interestingly, how these particular gene controls the ability to subsequently colonize distant organs depends on the organ-colonizing faculties of disseminated tumor cells rather than interaction with the restrictive microenvironment of target organs. Collectively, these results show that genes selected for metastasis contribute to the different steps and represent the random accumulation of traits that provide the necessary advantage for adaptation to a different organ microenvironment and need at any time.