Establishing orthotopic mestastatic breast cancer model for the study of immune response to a pancarcinoma markder PRSS14

초록

Establishing Orthotopic Mestastatic Breast Cancer Model for the Study immune response to an Pan Carcinoma Marker, PRSS14/Matriptase/St14 as a Tumor Self Antigen Ki Yeon Kim, Sauryang Kim, Noh Hyun Park, Binderya Ganzorig, and Moon Gyo Kim Inha University, Incheon, Korea PRSS14/Epithin/matriptase, a type II transmembrane serine protease is overexpressed in nearly all, if not all, human progressed epithelial cancers. Earlier we showed that it plays critical roles in angiogenesis, epithelial mesenchymal transition, transendothelial migration in vitro, as well as in mouse tumor metastasis in vivo. In order to understand the immune parameters during cancer progression and metastatic process, we utilize PRSS14 as a tumor self antigen and established two orthotopic mouse breast cancer models. When PRSS14 message was depleted, metastasis of 4T1 breast cancer cells was markedly reduced in the Balb/c. PRSS14 expressing E0771 breast cancer cells, showed higher metastasis than PRSS14 nonexpressing B16 melanoma in C57BL/6. Antigenic peptides derived from PRSS14 efficiently produced the specific antibodies of Th1 and/or Th2 with various adjuvants such as Complete Freund’s adjuvant, alum, MF59, and CpG, indicating that the responses against antitumor self antigen can be induced by breaking self-tolerance when it is conjugated. These antibodies efficiently inhibited the metastasis with two syngenic breast cancer models in antigen specific fashion since the scrambled sequence of the peptide failed to inhibit. These 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.