Study Of SIPA1-high Expressing Breast Cancer Cell-derived Exosomes Promoting The Metastasis Of Breast Cancer Cell

Tumor metastasis is one of the most important factors that lead to the rapid deterioration of the patient and poor prognosis.In addition to the biological characteristics of the tumor itself,exosomes secreted by tumor cells in tumor microenvironment can accelerate tumor development by promoting tumor angiogenesis and remodeling tumor microenvironment.SIPA1 molecule(signal-induced proliferation-associated protein 1)is a mitogen-induced GTPase activated protein,which has specific Rap GAP activity against Rap1 and Rap2 and can hydrolyse Rap GTP into Rap GDP.Studies have demonstrated that this protein can not only combine with other proteins to affect the physiological function of cells,but also play a very important role in maintaining the homeostasis of the immune system and regulating the cell cycle.Recent studies have further indicated that SIPA1 protein can accelerate the development process of tumor by regulating the adhesion and invasion of various cancers,but it is not completely clear whether SIPA1-high expressing tumor cells have a unique metastasis mechanism.This paper mainly focused on exosomes derived from SIPA1-high expressing breast cancer,and explored the specific mechanism of SIPA1 protein and exosomes in regulating breast cancer metastasis by establishing zebrafish breast cancer model.Firstly,breast cancer cells were labeled with green fluorescent dye Dio,and injected into the yolk sac of embryonic zebrafish by microinjection technique through xenotransplantation.Two days later,the distribution of breast cancer cells in zebrafish was observed and recorded by using fluorescence microscope The results demonstrated that breast cancer cells could still survive 48 hours after it was transplanted into zebrafish,it could migrate to the head,trunk and tail of the zebrafish through blood vessels,and most of the cancer cells migrate to the tail.In addition,compared with low metastatic MCF7 breast cancer cell,high metastatic MDA-MB-231 breast cancer cell had significantly more cells transferred to the tail.The above results indicate that the successful establishment of zebrafish breast cancer model can be used to explore the problems related to breast cancer cell metastasis.In order to investigate the effect of exosomes derived from breast cancer on the metastasis of breast cancer cell,the exosomes were first labeled with red fluorescent dye Dil,and injected into the yolk sac of embryonic zebrafish by microinjection.Two days later,the distribution of exosomes in zebrafish was observed and recorded by using fluorescence microscope.The results showed that exosomes could spread in zebrafish and migrate to the tail through blood vessels.At the same time,compared with exosomes with lower expression of SIPA1,the higher group had induced more intestinal angiogenesis of the zebrafish.In addition,when exosomes and breast cancer cells were mixed and injected into zebrafish,the exosomes with higher expression of SIPA1 would enhance the metastasis ability of breast cancer cells,thus enabling more breast cancer cells to migrate to the tail.The above results fully indicate that exosomes with high expression of SIPA1 play a very important role in promoting tumor angiogenesis and enhancing the metastasis ability of breast cancer cells.This also laid a foundation for further elucidating the mechanism of SIPA1 protein regulating tumor metastasis and clinical treatment of breast cancer.