The Influence of Cancer Associated Fibroblasts on the Growth of Pancreatic Neuroendocrine Tumors

Authors

• SV Yellapragada
• SD Forsythe
• JP Madigan
• SG Andrews
• SM Sadowski

Abstract

Pancreatic Neuroendocrine Tumors (PNETs) are rare neoplasms with rising incidence rates. Presently there are limited therapeutic options due to the unique and diverse biology of PNETs. The tumor microenvironment (TME) plays a role in altering tumor behavior through interactions between different cell populations. Among those populations are cancer associated fibroblasts (CAFs): a subgroup of stromal cells. Studies on other cancers showcase CAFs’ involvement in tumor cell growth and survival through secretion of growth factors. However, the roles of CAFs in the progression of PNETs are understudied preventing further understanding of PNET biology beneficial to therapy enhancement. To address this research gap, we analyzed the interaction between the two populations through a co-culture of patient derived CAFs (CAF 2 and CAF 3) conditioned media (FCM) and PNET cell lines (BON-1 and NT-18P) using cell proliferation assessments. Our results demonstrate a higher cell proliferation over seven days among FCM treated cells in comparison to cells grown in serum free control media (+73% for CAF 2, +78% for CAF 3). Additionally, BON-1 cells cultured in FCM demonstrated increased colony formation (CAF 2 =146 colonies, CAF 3 = 153 colonies) while no measurable colonies formed in the control. NT-18P cells demonstrated an increased number of proliferating cells in G2 mitotic state in FCM conditions (CAF 2= 26%, CAF 3= 14% vs Control= 11%). Further work to identify growth factors in the FCM contributing to our observations is ongoing. These results may lead to identification of biomarkers that serve as therapeutic targets against PNET development.

Scientific Focus Area: Cancer Biology

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