4.6 Article

IL-6 promotes drug resistance through formation of polyploid giant cancer cells and stromal fibroblast reprogramming

Journal

ONCOGENESIS
Volume 10, Issue 9, Pages -

Publisher

SPRINGERNATURE
DOI: 10.1038/s41389-021-00349-4

Keywords

-

Categories

Funding

  1. M. D. Anderson Cancer Center SPORE in Ovarian Cancer [P50CA217685]
  2. Moonshot program in ovarian cancer

Ask authors/readers for more resources

The research revealed that IL-6 plays a crucial role in the formation and transformation of PGCCs into CAFs, and blocking IL-6 can attenuate tumor growth and inhibit drug resistance.
To understand the role of polyploid giant cancer cells (PGCCs) in drug resistance and disease relapse, we examined the mRNA expression profile of PGCCs following treatment with paclitaxel in ovarian cancer cells. An acute activation of IL-6 dominated senescence-associated secretory phenotype lasted 2-3 weeks and declined during the termination phase of polyploidy. IL-6 activates embryonic stemness during the initiation of PGCCs and can reprogram normal fibroblasts into cancer-associated fibroblasts (CAFs) via increased collagen synthesis, activation of VEGF expression, and enrichment of CAFs and the GPR77 + /CD10 + fibroblast subpopulation. Blocking the IL-6 feedback loop with tocilizumab or apigenin prevented PGCC formation, attenuated embryonic stemness and the CAF phenotype, and inhibited tumor growth in a patient-derived xenograft high-grade serous ovarian carcinoma model. Thus, IL-6 derived by PGCCs is capable of reprogramming both cancer and stromal cells and contributes to the evolution and remodeling of cancer. Targeting IL-6 in PGCCs may represent a novel approach to combating drug resistance.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available