Abstract 295: Induction of senescent cancer associated fibroblasts promotes cancer cell growth

Abstract Cancer associated fibroblasts (CAF) are heterogenous and plastic population in the tumor microenvironment (TME), and each of the CAF subtypes plays a different role in cancer progression and suppression. Chemotherapy can induce CAF senescence, and cell senescence has been known to promote tumor growth and drug resistance. To investigate the role and molecular mechanism of the senescent CAF to promote tumor growth, we set up methods to induce CAF senescence by Chemotherapy or Radiation therapy using two gastrointestinal CAF cell lines CK4520 and CK8612. The flow cytometry showed around 40% of the cells with beta-gal staining in both CK8612 and CK4520 by the Etoposide (40 uM) treatment, and around 80-90% of the cells with beta-gal staining by the X-ray (20 Gy) treatment in both CK8612 and CK4520. Western blot assay showed an increase in p21 and p53 at protein level, and a decrease in Lamin B1 at the protein level in both CK8612 and CK4520 by the X-ray treatment. The cytokine profiling showed an increase in IL6, IL8, and CXCL2 and other factors related to senescence in CK4520 cells treated with X-ray and Etoposide. These results indicate the CAF senescence. In addition, the cytokine profiling also showed the different senescence-associated secretory phenotype (SASP) in CK4520 cells between X-ray and Etoposide treatment, and the different SASP also observed between CK4520 and CK8612 upon the X-ray treatment. To determine if the senescent CAF promotes tumor growth, we generated the conditioned medium using the senescent CK4520. Cancer cells cultured with the conditioned medium showed an increase in cell viability in different cancer cell lines. These results suggest that SASP of the senescent CAF promotes cancer cell growth. Citation Format: Shengliang Zhang, Lanlan Zhou, Leiqing Zhang, Wafik S. El-Deiry. Induction of senescent cancer associated fibroblasts promotes cancer cell growth [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 295.