Matrix metalloproteinase-2 delivery to extracellular vesicles produced by HPV-positive cervical cancer cells enhances metastasis via the Akt pathway

Cell Biol Int. 2023 Jun 5. doi: 10.1002/cbin.12054. Online ahead of print.ABSTRACTHere, we aimed to analyze the effects of matrix metalloproteinase-2 (MMP-2) delivery to extracellular vesicles (EVs) secreted by human papillomavirus (HPV)-associated cervical cancer cells on human umbilical vein endothelial cell (HUVEC) angiogenesis. First, MMP-2 expression was compared among SiHa (HPV16), HeLa (HPV18), and C-33A (negative) cells. Then, EVs were isolated from these cells, and MMP-2 expression in the EVs was compared. SiHa and HeLa cells were transfected with MMP-2 or control siRNA. HUVECs were treated with EVs isolating from transfected cells. Migration and angiogenesis of HUVECs were measured, and p-Akt protein expression in HUVECs was detected. An Akt inhibitor or activator was used to analyze the effect of MMP-2 delivery to EVs on the migration of HUVECs. The SiHa-induced xenograft tumors were treated with 2 µg of EVs every 3 d for a total of 27 d. Tumor growth, and the expression levels of p-Akt, MMP-2, and vascular endothelial growth factor (VEGF) were observed in the tumors. The results showed that MMP-2 expression was higher in SiHa- and HeLa-derived EVs than that in the C-33A-derived EVs. Interference with MMP-2 suppressed the invasion of SiHa and HeLa cells. The migration and angiogenesis of HUVECs were enhanced by MMP-2 delivery to EVs secreted by SiHa and HeLa cells through regulation of the Akt pathway. The growth of xenograft tumors was accelerated by EVs secreted...
Source: Cell Biology International - Category: Cytology Authors: Source Type: research