Establishment of Breast Cancer mouse models with Th1 and Th2 types for the study of cancer immunology

초록

In order to study the immune responses during tumor progression and metastatic process, we established two mouse breast cancer models using immunocompetent C57BL/6 and Balb/c mouse strains. The syngenic breast cancer cell lines used for C57BL/6 and Balb/c are EO771 and 4T1, respectively. By using a simple metastatic assay through tail vein injection, both cell lines showed strong metastasis to the lungs of their hosts. These cells were also orthotopically implanted into mammary fat pad and followed for primary tumor growth and metastasis as well as for the survival and necrosis. The cell lines consistently express PRSS14/Epithin that plays critical roles in cancer metastasis. When the cells lose their expression of PRSS14/Epithin by introducing shRNA, the growth rates of the primary tumor were much slower and the metastasis was diminished in both TH1 and TH2 type mouse strains. In addition, the initiation of the tumor necrosis appears slower and the survival rates were increased. When KLH conjugated antigenic peptides derived from PRSS14/Epithin were immunized with various adjuvants, the antigen specific antibodies were efficiently produced. The degrees in reduction of metastasis correlated to the level of TH2 type antibody responses in both C57BL/6 and Balb/c models, indicating TH2 response is responsible for reducing metastatic process. Alum and MF59 adjuvants revealed high TH2 type while CFA adjuvants produced TH1 type antibody responses in both mouse strains. These two different types of mouse models with their coupled breast cancer cell lines and the modification techniques for immune responses are useful for the study of mechanism of immune modulation against both cancer progression and metastasis.