Clinically relevant animal model of human breast cancer and VEGF involement in desmoplastic response

摘要

Expression of VEGF correlates with clinically aggressive, tamoxifen resistant metastatic breast cancers. To assess the role of VEGF expression on breast cancer growth, metastasis and development of anti-estrogen resistance, and desmoplasia an ER-positive, several MCF-7-derived cell lines, designated C9V, were engineered to express VEGF in a doxycycline-regulated manner. C9V cells were introduced into a athymic nude mouse to produce a xenograft model of breast cancer. Expression of VEGF in xenografts increased neoangiogenesis, enhanced tumor growth, stimulated a tamoxifen resistant phenotype, increased metastatic potential and induced a desmoplastic response. These results suggest that inhibition of VEGF expression or action will be effective in the treatment of breast cancer. In addition, inhibition of VEGF expression or action with inhibition of estrogen expression or action may also be effective.