Remodeling of hepatic stellate cells orchestrated the stroma-derived oxaliplatin-resistance through CCN3 paracrine in hepatocellular carcinoma
| Autor: | Fan Chang, Pengbo Ning, Ge Song, Xuelian Xiao, Yang Bu, Mei Zhang, Qingan Jia, Xia Liao, Fengan Jia |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
Cancer Research Carcinoma Hepatocellular Microenvironment Hepatocellular carcinoma Biology lcsh:RC254-282 Paracrine signalling Mice Nephroblastoma Overexpressed Protein Stroma Surgical oncology In vivo Cell Movement Hepatic stellate cells Cell Line Tumor Paracrine Communication Genetics medicine Tumor Microenvironment Animals Humans neoplasms Cell Proliferation Liver Neoplasms medicine.disease Prognosis lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Oxaliplatin resistance Actins digestive system diseases Up-Regulation Gene Expression Regulation Neoplastic Oxaliplatin Oncology Drug Resistance Neoplasm Cancer research Hepatic stellate cell Disease Progression Female Collagen Signal transduction Infiltration (medical) Neoplasm Transplantation Research Article CCN3 |
| Zdroj: | BMC Cancer, Vol 19, Iss 1, Pp 1-11 (2019) BMC Cancer |
| ISSN: | 1471-2407 |
| Popis: | Background Hepatic stellate cells (HSCs) have a key role in fibrogenesis and in the filtrates of the hepatocellular carcinoma (HCC) stroma, in which they are remodeled and play a critical role in HCC progression. However, the precise role of HSCs trending, infiltration and paracrine in orchestrating the stroma-derived oxaliplatin-resistance in HCC is still vague. Methods The chemo-resistant models were established to explore the correlation between HSC cells and the condition of chemoresistance. The HCC clinical samples were collected to confirm this phenomenon. Then, the relationship between secretory CCN3 from oxaliplatin-resistant HCC and the infiltration of HSCs in associated HCC microenvironment was evaluated. Finally, the role and mechanism of HSCs remodeling in the orchestration of oxaliplatin-resistant HCC were explored. Results The increased infiltration of HSCs and collagen accumulation were found in the microenvironment of oxaliplatin-resistant HCC. The cDNA profiles of the oxaliplatin-resistant HCC was reanalyzed, and CCN3 was one of the significantly increased genes. In HCC clinical samples, the levels of CCN3 and α-SMA are positively correlated, and high expression of CCN3 and α-SMA are positively associated with malignant phenotype and poor prognosis. Then the enhanced abilities of migration and proliferation of HSCs, and elevation of the cytokines paracrine from HSCs relating to HCC malignancy were proved in vitro and in vivo, and which were related to CCN3-ERK signaling pathway activation. Conclusions HSCs remodeling are positively related to CCN3 paracrine in hepatocellular carcinoma, which orchestrated the stroma-derived resistance to chemotherapy in HCC. |
| Databáze: | OpenAIRE |
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