Abstract
Zebrafish model have become a powerful tool in cancer research in recent years. The advantages of the zebrafish tumor xenograft model include: low cost, easy experimentation, reduced dosage for drug test, feasibility of various genetics/proteomics approaches such as whole mount in situ hybridization and whole mount immunocytochemistry. Different from other vertebrate organisms, the transparency of zebrafish embryo allowed us to monitor tumor progression and the tumor-induced angiogenesis in live embryos. In addition, zebrafish tumor xenograft model is much more rapid and cheaper than the current mouse model. Thus, here I aimed to use this model in tumor-induced angiogenesis research. Ovarian carcinoma is considered as one of the leading gynecologic cancers with high mortality rate. The tumor malignancy is highly associated with tumor-induced angiogenesis. The tumor-associated macrophages (TAMs) with M2-like phenotype have been reported with tumor malignancy by promoting tumor-induced angiogenesis; however, the mechanisms of the interaction between cancer cells and macrophages are incompletely understood. In this study, I established the zebrafish tumor xenograft model to accompany the in vitro cell-based assays to elucidate the molecular mechanism of tumor-induced angiogenesis in the cancer microenvironment. I have identified that the VEGFA and cathepsin S are induced in SKOV3 cells after co-cultured with M2-polarized macrophages. Furthermore, the zebrafish tumor xenograft model indicated when co-injected with M2-polarized macrophages, the tumor-induced angiogenesis was significantly increased. In conclusion, my results revealed that the tumor-associated macrophages could trigger the ovarian cancer cells to up-regulate angiogenesis-related genes in promoting tumor-induced angiogenesis.