Tumor-stromal cross-talk modulating the therapeutic response in pancreatic cancer

Hepatobiliary & Pancreatic Diseases International : HBPD INT
Christopher C M NeumannRosa Bianca Schmuck

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant solid tumor with a dismal prognosis. The stroma component makes up to 90% of the tumor mass and is thought to be one of the main reasons for the tumor's high chemoresistance. Cancer associated fibroblasts (CAFs) have previously been identified to be the key stromal players. This is the first time we provide detailed in vitro experiments investigating tumor-stromal interactions when exposed to three well-known chemotherapeutic agents. Monocultures, indirect and direct co-cultures of two PDAC cell lines (AsPC and Panc-1) and six primary patients derived CAFs were treated with gemcitabine, nab-paclitaxel and the γ-secretase-inhibitor (GSI) DAPT. The cell viability of each component was measured with XTT. Finally, IL-6 concentrations of the supernatants were analyzed. On the contrary to PDAC cell lines, CAF monocultures hardly responded to any treatment which suggested that stroma (CAFs) itself is more resistant to standard chemo-treatments than the epithelial cancer cells. Moreover, only a weak chemotherapeutic response was observed in direct co-cultures of cancer cells with CAFs. A change in the morphology of direct co-cultures was accompanied with the chemoresistance....Continue Reading

Citations

Feb 25, 2020·The American Journal of Surgical Pathology·Iván A GonzálezDeyali Chatterjee
Jan 11, 2020·Frontiers in Oncology·Wei MuMargot Zöller
Aug 18, 2020·Cancer Management and Research·Xiaobo Xu, Shusen Zheng
Aug 3, 2021·Frontiers in Cell and Developmental Biology·Xinglong GengBei Sun
Jul 15, 2021·Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract·Kasia Trebska-McGowanEvan S Glazer

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