Format

Send to

Choose Destination
Mol Cell Biol. 2019 Jan 3;39(2). pii: e00359-18. doi: 10.1128/MCB.00359-18. Print 2019 Jan 15.

Senescent Breast Luminal Cells Promote Carcinogenesis through Interleukin-8-Dependent Activation of Stromal Fibroblasts.

Author information

1
Department of Molecular Oncology, King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia.
2
The National Center for Stem Cell Technology, King Abdulaziz City for Science and Technology, Riyadh, Kingdom of Saudi Arabia.
3
Stem Cell & Tissue Re-Engineering Program, King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia.
4
Department of Molecular Oncology, King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia aboussekhra@kfshrc.edu.sa.

Abstract

Aging and stress promote senescence, which has intrinsic tumor suppressor functions and extrinsic tumor promoting properties. Therefore, it is of utmost importance to delineate the effects of senescence inducers on the various types of cells that compose the different organs. We show here that primary normal breast luminal (NBL) cells are more sensitive than their corresponding stromal fibroblasts to proliferative as well as oxidative damage-induced senescence. Like fibroblasts, senescent NBL cells secreted elevated amounts of various cytokines, including interleukin-6 (IL-6) and IL-8, and expressed high levels of p16, p21, and p53, while lamin B1 was downregulated. When senescent, luminal cells activated stromal fibroblasts in an IL-8-dependent manner, through the activation of the STAT3 pathway. These myofibroblasts promoted the epithelial-to-mesenchymal transition and the stemness processes in breast cancer cells in a paracrine manner both in vitro and in a breast cancer animal model. These results show the role of senescent breast luminal cells in promoting the inflammatory/carcinogenic microenvironment through the activation of fibroblasts in an IL-8-dependent manner.

KEYWORDS:

IL-8; breast cancer; fibroblasts; luminal cells; senescence

PMID:
30397077
PMCID:
PMC6321881
[Available on 2019-07-03]
DOI:
10.1128/MCB.00359-18

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center