Colorectal cancer (CRC) is one of the most common gastrointestinal malignancies, with the third highest incidence and the second highest mortality in all malignant tumors [1, 2]. Chemotherapy is the primary treatment for advanced metastatic tumors . However, multidrug resistance (MDR) often leads to poor efficacy of chemotherapy [3, 4]. The proliferation of drug-resistant cells is accelerated and metastases to distant regions, promoting increased angiogenesis . Clinically, it is often found that tumor cells have multi-drug resistance to a variety of chemotherapy drugs, resulting in tumor recurrence and tumor metastasis. Therefore, it is of great significance to explore the mechanism and treatment of tumor- resistant cells.
Exosomes are nanoscale vesicles with a diameter of 30-100nm secreted by a variety of living cells, which can be stable in body fluids and play the role of information transmission between cells . Exosomes contain a large number of maternal-cell-derived substances, including proteins, nucleic acids and lipids, which participate in the regulation of tumor microenvironment in the way of transmitting material information . It involved in tumor growth, invasion and metastasis, immune escape, chemotherapy resistance and radiotherapy tolerance [7, 8]. Studies on pancreatic ductal adenocarcinoma, breast cancer, ovarian cancer, liver cancer and lung cancer have all shown that exosome transport is involved in chemotherapy resistance [9–11]. Exosomes secreted by tumor cells and stromal cells enhanced and induced drug resistance in recipient cells by transferring their contents (DNA, mRNA, miRNA, Lnc RNA, protein, etc.) into recipient cells to alter their phenotype. However, few studies have focused on the effect of exosomes on tumor angiogenesis, especially in colon cancer.
Bone morphogenetic protein 2 (BMP-2) is a highly closed live opalics contained in the family of transgenic growth factor-β (TGF-β) . The main biological function of BMP-2 is to regulate cell proliferation, chemotaxis and apoptosis, which is closely related to the growth and development of embryos, aging and canceration . Studies have shown that BMP2 is involved in the process of apoptosis, migration and invasion of CRC, liver cancer, gastric cancer and lung cancer [13–15], and affects the release of immune factors by tumor cells. Feng et al. found that BMP2 was highly expressed in liver cancer tissues . Overexpression of BMP2 promoted cell proliferation, migration, invasion, microvascular density and angiogenesis, and reduce cell apoptosis . However, the role of BMP-2 in drug resistance and angiogenesis is not fully understood.
In this study, we investigated the relationship between drug resistance and angiogenesis in human colon cancer SW480 cells. In addition, we also determined the role of SW480 cancer cell exosomes in angiogenesis and its potential mechanism.