Abstract 6834: Periostin involvement in cellular senescence in ovarian cancer

Abstract

Abstract Purpose: Despite improvements in care and advancements in the understanding of ovarian cancer (OC) pathobiology and genetics, survival rates remain disappointingly low compared to other types of cancer. This is due to a lack of diagnosis strategies, high recurrence rates, and the development of chemo-resistant diseases, which require synergy between cancer cells and the tumor microenvironment (TME). We have demonstrated the functional importance of a TME gene, periostin (POSTN), in OC and recurrent OC, using in vitro and in vivo models. Our objectives were to identify differentially expressed genes by POSTN expression in the TME that contribute to the progression of ovarian cancers. Procedures: Gene expression data was generated from an ovarian cancer cell line, HEYA8, cultured in a high POSTN conditioned 3D cell culture environment, using the NovaSeq 6000 system to generate RNA-seq data. The data was analyzed to determine the genes expressed at different levels between the HEYA8 cells grown with or without POSTN-high conditioned medium (CM). The gene functional annotation and KEGG pathway enrichment were further analyzed from 10,115 significant differentially expressed genes between the HEYA8 cells grown in high levels of POSTN (CMPOSTNhigh) or low levels of POSTN (CMCTL) culture conditions, using DAVID bioinformatics. Results: Using a cell culture and co-culture model, we found that OC cells cultured under conditioned media containing CMPOSTNhigh exhibited faster cell migration, more invasiveness (p=0.006), more chemo-resistance (p<0.05), and increased resistance to paclitaxel-induced apoptosis, compared to OC cells cultured with control medium (CMCTL). OC cell lines cultured with CMPOSTNhigh showed increased side population cells relative to CMCTL -cultured cells, suggesting POSTN plays important roles in cancer stem cell enrichment. POSTN-transfected 3T3-L1 cells exhibited more intracellular and extracellular lipids and were linked to increased cancer cell expression of the oncogene fatty acid synthetase. In correspondence to the functions of POSTN in OC cells, the pathways identified to be significantly impacted by POSTN expression included, but were not limited to, the cell cycle, apoptosis, p53 signaling, MAPK signaling, and PI3K-Akt signaling pathways. Interestingly, we also found cellular senescence pathways was one of the most significantly impacted by POSTN suggesting that POSTN may play roles in ovarian cancer via the regulation of cellular senescence, which has not yet been explored. Conclusions: These data emphasize the importance of TME factors in tumor progression and prognosis via various ways in ovarian cancer, establishing promising potential therapeutic targets of OC. Citation Format: Jihua Feng, Ethan Nguyen, Jocelyn Reyes, Zhiqing Huang. Periostin involvement in cellular senescence in ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6834.