Abstract LB-278: Cancer stem cells as the novel origin of cancer-associated fibroblast-like cells

Abstract

Abstract Cancer associated fibroblast (CAF) is an indispensible component of stromal microenvironment mediating cancer progression notably in breast, prostate and pancreatic carcinoma. CAF heterogeneity is attributed to its possible multiple origin majorly from tumor resident fibroblast, mesenchymal stem cells, epithelial cells. The present work analyses the possibility of cancer stem cells (CSC) as the source of CAF like cells. For this, we have used the model of CSC established in our laboratory derived from mouse induced pluripotent cells (miPSCs) by culturing with conditioned medium from cancer cell lines mimicking tumor microenvironment. In the present study, human breast cancer derived T47D and BT549 cells have been cultured to collect the conditioned medium. Since the green fluorescent protein (GFP) gene was integrated under the control of Nanog promoter in the miPSCs used in this study, the resulting CSCs was assessed by the expression of GFP for the undifferentiated state. The differentiation of CSCs was tracked by the attenuation of GFP. The CSC population was multiplied by serial subcutaneous and orthotropic transplantation in nude mice. This population was further enriched by sphere formation. Then these spheres were allowed to differentiate into adhesive cells. The CAF-like cells were separated from the differentiated population. The expression of prominent CAF markers fibroblast specific protein (FSP), fibroblast activation protein (FAP), vimentin, collagen type1 α1, and smooth muscle actin (SMA) were assessed by real time PCR. Immuno-cytochemistry of the cells for the expression of FSP, FAP and SMA was further confirmed for the evidence that cancer stem cells should be a possible source of CAF. This model should elaborate the functional heterogeneity amongst CAFs and help design therapeutic interventions to inhibit such conversions. Citation Format: Neha Nair, Arun Vaidyanath, Kenta Hoshikawa, Anna Sanchez Calle, Tomonari Kasai, Masaharu Seno. Cancer stem cells as the novel origin of cancer-associated fibroblast-like cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-278.