Interleukin-8 Dedifferentiates Primary Human Luminal Cells to Multipotent Stem Cells.

ABSTRACT: During aging, cellular plasticity and senescence play important roles in tissue regeneration and the pathogenesis of different diseases, including cancer. We have recently shown that senescent breast luminal cells can activate their adjacent stromal fibroblasts. In the present report, we present clear evidence that these senescence-related active fibroblasts can dedifferentiate proliferating primary human luminal cells to multipotent stem cells in an interleukin-8 (IL-8)-dependent manner. This was confirmed using recombinant IL-8, while the truncated protein was not active. This IL-8-related dedifferentiation of luminal cells was mediated through the STAT3-dependent downregulation of p16INK4A and the microRNA miR-141. Importantly, these in vitro-generated mammary stem cells exhibited high

SUBMITTER: Al-Khalaf HH 

PROVIDER: S-EPMC7156216 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature