Efficient Th2 Immune response can Inhibit Cancer metastasis

초록

Efficient Th2 Immune Response can Inhibit Cancer Metastasis Ki Yeon Kim, Binderya Ganzorig, Sau Ryang Kim, and Moon Gyo Kim* Department of Biological sciences, Inha University PRSS14/Epithin/matriptase is a type II transmembrane serine protease that is over expressed in progressed epithelial cancers. Our previous studies showed its critical roles in angiogenesis, epithelial mesenchymal transition, transendothelial migration in vitro, as well as tumor metastasis in vivo. In order to study the immune parameters during cancer progression and metastatic process, we utilize PRSS14 as a model tumor antigen in two mouse breast cancer models. Several antigenic peptides derived from PRSS14 were first tested for the production of antibodies. When peptides were conjugated with carrier KLH and injected with various adjuvants, high titer specific antibodies were generated, indicating that responses against antitumor self antigen can be induced by breaking self-tolerance. These antibodies efficiently inhibited the metastasis with 4T1 breast cancer model in Balb/c mouse in PRSS14 specific fashion since the scrambled sequence of the peptide failed to inhibit. The specific peptide immunized mice showed the high titer antibody responses that showed the Th2 isotype bias. In addition, a new mouse breast cancer model was established in C57BL/6 mouse strain that is known as a domestic Th1 type immune response host. The results show that the selected peptide with proper adjuvants can be used as a preventive cancer metastasis vaccine in both Th2 type Balb/c and Th1 type C57BL/6 hosts. Using various adjuvants with different Th types are now under being investigated for the study of mechanism of metastasis inhibition. Keyword: PRSS14/Epithin/matriptase, Metastasis vaccine, Immune response, Breast cancer, Lung metastasis