Hang Wang1, Miqing Yang1, Ling Lin1, Hongzhen Ren1, Chaotong Lin1, Suling Lin1, Guoying Shen1, Binfeng Ji1, Chun Meng2,3. 1. Institute of Pharmaceutical Biotechnology and Engineering, College of Biological Science and Biotechnology, Fuzhou University, Fuzhou, Fujian, 350108, China. 2. Institute of Pharmaceutical Biotechnology and Engineering, College of Biological Science and Biotechnology, Fuzhou University, Fuzhou, Fujian, 350108, China. mengchun@fzu.edu.cn. 3. , Qi Shan Campus, 2 Xue Yuan Road, University Town, Fuzhou, Fujian, 350108, People's Republic of China. mengchun@fzu.edu.cn.
Abstract
BACKGROUND: The presence of cancer stem cells (CSCs) is currently regarded as one of the main culprits of tumor formation and therapy failure. It is known that chronic inflammation is associated with CSCs, but it is not clear yet how inflammation affects the development of CSCs. In the present study we aimed to examine the relationship between cancer cell stimulation mediated by immune cells and the acquisition of a CSC-like phenotype. METHODS: Cancer cells derived from single hepatocarcinoma HepG2 cells were treated with mouse splenic B cells (MSBCs) and mouse peritoneal macrophage cells (MPMCs), respectively. The stem cell-like characteristics of the resulting HepG2 cells (MSBC-HepG2 and MPMC-HepG2) were evaluated using different assays, including biomarker assays, in vitro tumoroid and colony forming assays, in vivo tumor forming assays and signal transduction pathway activation assays. RESULTS: Various stemness characteristics of HepG2 cells, including self-renewal, proliferation, chemoresistance and tumorigenicity were evaluated. The expression levels of stemness-related genes and its encoded proteins in the MSBC-HepG2 and MPMC-HepG2 cells were assessed using RT-PCR and FACS analyses. We found that MSBC-HepG2 and MPMC-HepG2 cells possess hepatic CSC properties, including persistent self-renewal, extensive proliferation, drug resistance, high tumorigenic capacity and over-expression of CSC-related genes and proteins (i.e., EpCAM, ALDH, CD133 and CD44), compared to the parental cells. We also found that 1x10(3) MSBC-HepG2 and MPMC-HepG2 cells were able to form tumors in NOD/SCID mice and that the Notch and SHH signaling pathways were highly activated in MSBC-HepG2 cells. CONCLUSIONS: We conclude that the immune system may have a double-edge effect on cancer development. On one hand, immune cells such as B lymphocytes and macrophages may recognize, attack and eliminate cancer cells, whereas on the other hand, they may promote a subset of cancer cells to acquire stem cell-like characteristics.
BACKGROUND: The presence of cancer stem cells (CSCs) is currently regarded as one of the main culprits of tumor formation and therapy failure. It is known that chronic inflammation is associated with CSCs, but it is not clear yet how inflammation affects the development of CSCs. In the present study we aimed to examine the relationship between cancer cell stimulation mediated by immune cells and the acquisition of a CSC-like phenotype. METHODS:Cancer cells derived from single hepatocarcinoma HepG2 cells were treated with mouse splenic B cells (MSBCs) and mouse peritoneal macrophage cells (MPMCs), respectively. The stem cell-like characteristics of the resulting HepG2 cells (MSBC-HepG2 and MPMC-HepG2) were evaluated using different assays, including biomarker assays, in vitro tumoroid and colony forming assays, in vivo tumor forming assays and signal transduction pathway activation assays. RESULTS: Various stemness characteristics of HepG2 cells, including self-renewal, proliferation, chemoresistance and tumorigenicity were evaluated. The expression levels of stemness-related genes and its encoded proteins in the MSBC-HepG2 and MPMC-HepG2 cells were assessed using RT-PCR and FACS analyses. We found that MSBC-HepG2 and MPMC-HepG2 cells possess hepatic CSC properties, including persistent self-renewal, extensive proliferation, drug resistance, high tumorigenic capacity and over-expression of CSC-related genes and proteins (i.e., EpCAM, ALDH, CD133 and CD44), compared to the parental cells. We also found that 1x10(3) MSBC-HepG2 and MPMC-HepG2 cells were able to form tumors in NOD/SCIDmice and that the Notch and SHH signaling pathways were highly activated in MSBC-HepG2 cells. CONCLUSIONS: We conclude that the immune system may have a double-edge effect on cancer development. On one hand, immune cells such as B lymphocytes and macrophages may recognize, attack and eliminate cancer cells, whereas on the other hand, they may promote a subset of cancer cells to acquire stem cell-like characteristics.
Entities:
Keywords:
Cancer stem cells; HepG2 cells; Peritoneal macrophage cells; Splenic B cells
Authors: O Felthaus; T Ettl; M Gosau; O Driemel; G Brockhoff; A Reck; K Zeitler; M Hautmann; T E Reichert; G Schmalz; C Morsczeck Journal: Biochem Biophys Res Commun Date: 2011-02-20 Impact factor: 3.575
Authors: Xuan Sun; Robert C G Martin; Qianqian Zheng; Russell Farmer; Harshul Pandit; Xuanyi Li; Kevin Jacob; Jian Suo; Yan Li Journal: Cell Oncol (Dordr) Date: 2018-08-16 Impact factor: 6.730