AUTHOR=Zhang Xianbin , Schönrogge Maria , Eichberg Johanna , Wendt Edgar Heinz Uwe , Kumstel Simone , Stenzel Jan , Lindner Tobias , Jaster Robert , Krause Bernd Joachim , Vollmar Brigitte , Zechner Dietmar TITLE=Blocking Autophagy in Cancer-Associated Fibroblasts Supports Chemotherapy of Pancreatic Cancer Cells JOURNAL=Frontiers in Oncology VOLUME=8 YEAR=2018 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2018.00590 DOI=10.3389/fonc.2018.00590 ISSN=2234-943X ABSTRACT=

In this study we evaluated the interaction of pancreatic cancer cells, cancer-associated fibroblasts, and distinct drugs such as α-cyano-4-hydroxycinnamate, metformin, and gemcitabine. We observed that α-cyano-4-hydroxycinnamate as monotherapy or in combination with metformin could significantly induce collagen I deposition within the stromal reaction. Subsequently, we demonstrated that cancer-associated fibroblasts impaired the anti-proliferation efficacy of α-cyano-4-hydroxycinnamate, metformin and gemcitabine. Interestingly, inhibition of autophagy in these fibroblasts can augment the anti-proliferation effect of these chemotherapeutics in vitro and can reduce the tumor weight in a syngeneic pancreatic cancer model. These results suggest that inhibiting autophagy in cancer-associated fibroblasts may contribute to strategies targeting cancer.