Article: Differential capacity of CD90+ cells in autophagy activation following chemotherapy in hepatocellular carcinoma.
2020 Volume 19, Issue 6, Page(s) 645–652
Abstract: Introduction and objectives: Analysis of cancer biomarkers is an important tool in developing targeted-therapy and in modulating chemoresistance. Here, we analyze the relevance of CD90, a marker of cancer stem cells (CSC) in hepatocellular carcinoma ( ... ...
| Abstract | Introduction and objectives: Analysis of cancer biomarkers is an important tool in developing targeted-therapy and in modulating chemoresistance. Here, we analyze the relevance of CD90, a marker of cancer stem cells (CSC) in hepatocellular carcinoma (HCC) and its correlation with autophagy. Materials and methods: For in vivo study, 86 specimens were collected from 43 patients undergoing liver resections. In each patient, HCC nodule (HCC) and surrounding non-tumor (SNT) were collected. For in vitro study, HCC cells JHH6 subpopulations expressing CD90+ and CD90- were isolated using magnetic-sorter and confirmed by flow-cytometry. Upon doxorubicin treatment, autophagy turn-over was analyzed by RTqPCR for mRNA expression, Western blot for protein expression, and autophagosome staining for autophagy-flux. Cytotoxicity test was performed by MTT assay. Gene and protein analysis were performed in clinical samples together with immunohistostaining. Results: CD90 mRNA expression was higher in HCC than in SNT for 8-fold (p < 0.001). LC3-II protein was up-regulated in the HCC in comparison with the SNT (p < 0.05). In vitro model showed that CD90+ and CD90- cells had diverse expressions of autophagy-related genes. Upon doxorubicin treatment, autophagy was activated in both cells by increasing LC3-II protein expression, autophagic vacuoles, and dysregulation of autophagy-related mRNAs. A differential autophagic capacity was noticed between two subpopulations and it was correlated with cellular toxicity assay. Conclusions: We demonstrated the relevance of differential autophagy capacity of CD90+ cells in HCC. Autophagy was involved in cancer-defense mechanism against doxorubicin. Cancer promoting function of autophagy in CD90+ cells was also related to cancer environment. |
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| MeSH term(s) | Antibiotics, Antineoplastic/therapeutic use ; Autophagy/drug effects ; Carcinoma, Hepatocellular/drug therapy ; Carcinoma, Hepatocellular/metabolism ; Carcinoma, Hepatocellular/pathology ; Cell Culture Techniques ; Cell Line, Tumor ; Doxorubicin/therapeutic use ; Female ; Humans ; Liver Neoplasms/drug therapy ; Liver Neoplasms/metabolism ; Liver Neoplasms/pathology ; Male ; Microtubule-Associated Proteins/metabolism ; Middle Aged ; Thy-1 Antigens/metabolism | |||||
| Chemical Substances | Antibiotics, Antineoplastic ; MAP1LC3B protein, human ; Microtubule-Associated Proteins ; Thy-1 Antigens ; Doxorubicin (80168379AG) | |||||
| Language | English | |||||
| Publishing date | 2020-08-01 | |||||
| Publishing country | Mexico | |||||
| Document type | Journal Article ; Research Support, Non-U.S. Gov't | |||||
| ZDB-ID | 2188733-0 | |||||
| ISSN | 1665-2681 | |||||
| ISSN | 1665-2681 | |||||
| DOI | 10.1016/j.aohep.2020.07.007 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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