大鼠骨髓间充质干细胞来源外泌体促进结直肠癌干细胞增殖、侵袭和转移并抑制其凋亡

To evaluate the impact of exosomes derived from rat bone marrow mesenchymal stem cells (BM-MSCs) on the malignant properties of human colorectal cancer stem cells (CRC-CSCs) and the underlying mechanism involving epithelial-mesenchymal transition (EMT).

Exosomes were isolated and characterized from rat BM-MSCs. Human CRC-CSCs were enriched from HCT116 cells and subsequently treated with the exosomes. Cellular functions, including proliferation, apoptosis, cell cycle progression, migration, and invasion, were assessed using cell counting kit-8 (CCK-8), colony formation, flow cytometry, and Transwell assays, respectively. In vivo tumorigenicity and lung metastasis were evaluated using a xenograft mouse model. Expression levels of EMT markers (E-cadherin, N-cadherin, and Vimentin) were analyzed by western blot, qPCR, and immunofluorescence.

BM-MSCs-derived exosomes were efficiently internalized by HCT116-CSCs. In vitro, exosome treatment significantly enhanced cell proliferation, migration, invasion, and cell cycle progression, while suppressing apoptosis. In vivo, exosomes promoted tumor growth and lung metastasis. Mechanistically, exosome exposure induced EMT, as evidenced by decreased E-cadherin expression and increased expression of N-cadherin and vimentin in both in vitro and in vivo models.

Exosomes derived from rat BM-MSCs enhance the malignant phenotype and suppress apoptosis in human CRC-CSCs through the activation of the EMT pathway. These findings underscore the potential role of BM-MSC-derived exosomes in tumor microenvironment (TME) regulation and highlight their relevance as a potential therapeutic target.