Development And Study Of Orthotopic And Metastatic Mouse Models Of Breast Cancer With "Human Microenvironment"

The in vivo studies of breast cancer heavily rely on the availability of the experimental mouse models. An ideal orthotopic and metastatic mouse model of breast cancer is not only required to mimic the whole processes of tumor development and metastasis, but also required to provide"human tissue microenvironment"for the breast cancer cells to proliferate and metastasize. Several mouse models have been introduced in literature but failed to achieve the two requirements simultaneously. In this study, we developed a novel human breast tissue-derived orthotopic mouse model of breast cancer——"breast-breast"mouse model, in which the normal human breast tissues were implanted subcutaneously into severe combined immunodeficient (SCID) mouse to create a normal human mammary microenvironment, then the human breast cancer cells were inoculated into the implants. Pathologic examination showed that human breast cancer cells proliferated well in the implanted human breast tissues, and finally metastasized preferentially to the contralaterally implanted human breast tissues. Based on this model, we developed a series of"breast-organ"mouse models. Human breast tissues and human bone/lung/liver tissues were implanted into the left and right flanks of the SCID mice. After then, human breast cancer cells were inoculated into the left implanted human breast tissues. Pathologic examination showed that human bone and liver tissues survived well in SCID mice, while human lung tissues could not survive. In"breast-bone"and"breast-liver"mouse models, MDA-MB-231 did not metastasize to human bone and liver tissues, which indicated that MDA-MB-231 do not have the characteristics of bone and liver metastases."Breast-organ"mouse models of breast cancer not only provide the"human tissue microenvironment"for the proliferation and metastasis of human breast cancer cells, but also mimic the whole clinical processes of tumor development and metastasis. Consequently, they provide a good platform for the mechanic research of human breast cancer.