Cited by Metabolic reprogramming in cholangiocarcinoma

CAFs shape myeloid‐derived suppressor cells to promote stemness of intrahepatic cholangiocarcinoma through 5‐lipoxygenase DOI

Yuli Lin, Qian Cai, Yu Chen

и другие.

Hepatology, Год журнала: 2021, Номер 75(1), С. 28 - 42

Опубликована: Авг. 13, 2021

Abstract Background and Aims We previously demonstrated that cancer‐associated fibroblasts (CAFs) promote tumor growth through recruitment of myeloid‐derived suppressor cells (MDSCs). 5‐lipoxygenase (5‐LO) is highly expressed in myeloid critical for synthesizing leukotriene B4 (LTB4), which involved progression by activating its receptor type 2 (BLT2). In this study, we investigated whether how CAFs regulate MDSC function to enhance cancer stemness, the driving force aggressiveness chemotherapy refractoriness, desmoplastic intrahepatic cholangiocarcinoma (ICC). Approach Results RNA‐sequencing analysis revealed enriched metabolic pathways but decreased inflammatory MDSCs compared with blood from patients ICC. Co‐injection ICC patient‐derived promoted stemness an orthotopic model, was blunted depletion. Conditioned media (CM) CAF‐educated drastically tumorsphere formation efficiency marker gene expression cells. CAF‐CM stimulation increased activity 5‐LO MDSCs, while inhibitor impaired stemness‐enhancing capacity vitro vivo. Furthermore, IL‐6 IL‐33 primarily mediated hyperactivated metabolism MDSCs. identified LTB4‐BLT2 axis as downstream metabolite signaling promoting treatment LTB4 elevated or blockade BLT2 (which preferentially stem‐like cells) significantly reduced effects Finally, augmented chemotherapeutic efficacy xenograft models. Conclusions Our study reveals a role orchestrating optimal microenvironment educating suggests 5‐LO/LTB4‐BLT2 promising therapeutic targets chemoresistance targeting stemness.

Язык: Английский

Процитировано

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Mitochondrial oxidative metabolism contributes to a cancer stem cell phenotype in cholangiocarcinoma DOI