Modeling Pancreatic Cancer with Patient-Derived Organoids Integrating Cancer-Associated Fibroblasts.

Autor: Go YH; Department of Microbiology, CHA University School of Medicine, Seongnam 13488, Korea.; CHA Organoid Research Center, CHA University, Seongnam 13488, Korea., Choi WH; Department of Microbiology, CHA University School of Medicine, Seongnam 13488, Korea.; CHA Organoid Research Center, CHA University, Seongnam 13488, Korea.; R&D Institute, ORGANOIDSCIENCES Ltd., Seongnam 13488, Korea., Bae WJ; Department of Pathology, Ajou University School of Medicine, Suwon 16499, Korea., Jung SI; Department of Microbiology, CHA University School of Medicine, Seongnam 13488, Korea.; CHA Organoid Research Center, CHA University, Seongnam 13488, Korea., Cho CH; R&D Institute, ORGANOIDSCIENCES Ltd., Seongnam 13488, Korea., Lee SA; Department of Surgery, CHA Bundang Medical Center, CHA University, Seongnam 13496, Korea., Park JS; Pancreatobiliary Cancer Clinic, Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Korea., Ahn JM; Department of Pathology, Ajou University School of Medicine, Suwon 16499, Korea., Kim SW; Department of Otolaryngology-Head and Neck Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea., Lee KJ; R&D Institute, ORGANOIDSCIENCES Ltd., Seongnam 13488, Korea., Lee D; Department of Pathology, Ajou University School of Medicine, Suwon 16499, Korea., Yoo J; Department of Microbiology, CHA University School of Medicine, Seongnam 13488, Korea.; CHA Organoid Research Center, CHA University, Seongnam 13488, Korea.; R&D Institute, ORGANOIDSCIENCES Ltd., Seongnam 13488, Korea.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2022 Apr 21; Vol. 14 (9). Date of Electronic Publication: 2022 Apr 21.
DOI: 10.3390/cancers14092077
Abstrakt: Pancreatic cancer is a devastating disease and is highly resistant to anticancer drugs because of its complex microenvironment. Cancer-associated fibroblasts (CAFs) are an important source of extracellular matrix (ECM) components, which alter the physical and chemical properties of pancreatic tissue, thus impairing effective intratumoral drug delivery and resulting in resistance to conventional chemotherapy. The objective of this study was to develop a new cancer organoid model, including a fibrous tumor microenvironment (TME) using CAFs. The CAF-integrated pancreatic cancer organoid (CIPCO) model developed in this study histologically mimicked human pancreatic cancer and included ECM production by CAFs. The cancer cell-CAF interaction in the CIPCO promoted epithelial-mesenchymal transition of cancer cells, which was reversed by CAF inhibition using all-trans retinoic acid. Deposition of newly synthesized collagen I in the CIPCO disturbed the delivery of gemcitabine to cancer cells, and treatment with collagenase increased the cytotoxic effect of gemcitabine. This model may lead to the development of next-generation cancer organoid models recapitulating the fibrous TME.
Databáze: MEDLINE
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