Periostin facilitates ovarian cancer recurrence by enhancing cancer stemness

Abstract

Abstract The high lethality of Ovarian cancer (OC) is due to high recurrence and development of chemo-resistance, which requires synergy between cancer cells and tumor microenvironment (TME). Analysis of gene microarray from paired primary and recurrent OC tissues revealed significantly elevated expression of the gene encoding periostin (POSTN) in recurrent OC compared to matched primary tumors (p = 0.014). OC cells cultured with conditioned media with high levels of POSTN (CMPOSTNhigh) exhibited faster migration, more invasiveness (p = 0.006), and more chemoresistance (p < 0.05) compared to OC cells cultured with control medium (CMCTL). Furthermore, CMPOSTNhigh-cultured HEYA8 cells demonstrated increased resistance to paxlitaxel-induced apoptosis. OC cell lines cultured with CMPOSTNhigh showed increases in stem cell side population relative to CMCTL-cultured cells. POSTN-transfected 3T3-L1 cells exhibited more intracellular and extracellular lipids and was linked to increased cancer cell expression of the oncogene fatty acid synthetase. Additionally, POSTN functions in the TME were linked to AKT pathway activities. In a xenograft mouse model of OC, the mean tumor volume in mice injected with CMPOSTNhigh-grown OC cells was larger than that in mice injected with CMCTL-grown OC cells (p = 0.0023). Our results bolster the need for further study of POSTN as a potential therapeutic target and potential prevention of recurrent OC.