Pancreatic ductal adenocarcinoma (PDAC) continues to be one of the most lethal malignancies worldwide and responds poorly to current therapeutic modalities. Due to its late stage diagnosis and limited response to current treatments, it is imperative to develop novel and effective therapies for PDAC. Dense fibrotic stroma associated with PDAC abrogates drug perfusion into the tumor and activated pancreatic stellate cells (PSCs) are the major stromal cells responsible for stromal reaction. Furthermore, activated PSCs are known to secrete various factors causing autocrine effects to elicit sustained PSC activation and paracrine effects on cancer cells to promote tumor progression. Our previous work has shown that loss of miR-29 is a common phenomenon of both activated PSCs and pancreatic cancer cells, and its restored expression reduces stromal accumulation and cancer growth. In addition, conditioned media from miR-29 overexpressing PSCs reduces cancer cell viability. To extend our work on the role of miR-29 in tumor-stromal interactions, we examined how autocrine and paracrine signaling is affected by miR-29 overexpression in PSCs and cancer cells. We collected the conditioned media from miR-29a overexpressing human PSCs (hPSC-CM) or cancer cells (CC-CM) and cultured nascent PSCs or cancer cells to evaluate autocrine and paracrine effects. hPSCs and PDAC cells cultured in miR-29 hPSC-CM resulted in a significant reduction of cell viability. Likewise, miR-29 overexpressing CC-CM reduced the viability of hPSCs and cancer cells. Additionally, cancer cell migration was reduced when treated with miR-29 overexpressing hPSC- and CC-CM. Taken together, our results demonstrate that conditioned media collected from miR-29 overexpressing hPSCs and cancer cells reduces hPSC/cancer cell viability and cancer cell migration. Moreover, our findings highlight the important role of miR-29 in the autocrine/paracrine interactions between PSCs and cancer cells. In our future studies, we expect to identify the key factors that are regulated by miR-29 in tumor-stromal interactions.

Citation Format: Tricia Factora, Elise Briscoe, Jason Kwon, Janaiah Kota. Autocrine and paracrine effects of miR-29 in hPSCs and PDAC cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4490.