Cancer as a Disease of Self-Seeding

Abstract

Our work focuses on breast cancer metastatic suppressor genes and their functions in the metastatic process. For this, we are using breast cancer cell line model and their derivatives, 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. 1. American_Cancer_Society. Cancer facts and figures. American Cancer