Open AccessEnhanced expression of cyclooxygenase‐2 related multi‐drug resistance gene in melanoma and osteosarcoma cell lines by TSG‐6 secreted from canine adipose‐derived mesenchymal stem/stromal cells
Author(s) -
Yang SeJin,
An JuHyun,
Park SuMin,
Lee JeongHwa,
Chae HyungKyu,
Lee KyungMi,
Song WooJin,
Youn HwaYoung
Publication year - 2021
Publication title -
veterinary medicine and science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.485
H-Index - 11
ISSN - 2053-1095
DOI - 10.1002/vms3.442
Subject(s) - osteosarcoma , stromal cell , mesenchymal stem cell , cancer research , biology , transfection , cell culture , gene expression , gene , microbiology and biotechnology , genetics
Background Multiple drug resistance (MDR) of cancer cells is the main cause of intrinsic or acquired desensitization to chemotherapy in many cancers. A number of studies have found high expression of COX‐2 to be a factor for expression of MDR gene in several cancer. Furthermore, adipose tissue derived mesenchymal stem/stromal cells (ADSC) have been found to increase cyclo‐oxygenase‐2 (COX‐2) expression in some tumour cells. The mechanism for this, however, is not yet clear and needs further study. Objective The purpose of this study was to determine whether tumour necrosis factor‐alpha stimulated gene/protein 6 (TSG‐6) secreted from ADSCs is associated with an increase in MDR genes by inducing COX‐2 gene expression in melanoma and osteosarcoma cell lines. Methods ADSCs were transfected with TSG‐6 siRNA or Control RNA respected, and cancer cell line were transfected with COX‐2 siRNA or Control RNA respected. Using trans well coculture system, the interactions of ADSCs with tumour cells were investigated. Results Increased COX‐2 expression was observed in cancer cell co‐cultured with ADSCs. Additionally, we identified that COX‐2 expression was related to drug resistance genes (P‐glycoprotein, multidrug resistance‐associated protein). Transfecting canine ADSCs with small interfering RNA, TSG‐6 secreted from ADSCs was found to be a major factor in the regulation of COX‐2 expression and drug resistance genes in osteosarcoma and melanoma cell lines. Conclusion TSG‐6 mediated COX‐2 up‐regulation is a possible mechanism of chemoresistance development induced by ADSCs. These findings provide better understanding about the mechanism associated with ADSC‐induced chemoresistance in cancer.