The senescent microenvironment promotes the emergence of heterogeneous cancer stem-like cells

We reported previously that human epithelial cells that undergo telomere-driven chromosome instability (T-CIN) display global microRNA (miR) deregulation and develop migration and invasion capacities. Here, we show that post-crisis cells are not able to form tumors unless a senescent microenvironment is provided. The characterization of cell lines established from such tumors revealed that these cells have acquired cell autonomous tumorigenicity, giving rise to heterogeneous tumors. Further experiments demonstrate that explanted cells, while displaying differences in cell differentiation markers, are all endowed of enhanced stem cell properties including self-renewal and multilineage differentiation capacity. Treatments of T-CIN+ cells with senescence-conditioned media induce sphere formation exclusively in cells with senescence-associated tumorigenicity, a capacity that depends on miR-145 repression. These results indicate that the senescent microenvironment, while promoting further transdifferentiations in cells with genome instability, is able to propel the progression of premalignant cells towards a malignant, cell stem-like state.

Source: Carcinogenesis - September 30, 2015 Category: Cancer & Oncology Authors: Castro-Vega, L. J., Jouravleva, K., Ortiz-Montero, P., Liu, W.-Y., Galeano, J. L., Romero, M., Popova, T., Bacchetti, S., Vernot, J. P., Londono-Vallejo, A. Tags: Original Manuscript Source Type: research