Immunization of antigenic peptide from PRSS14/eppithin sequence interfere smetastasis of 4T1 breaast cancer in sequence specific fashioon

초록

PRSS14/Epithin, a type II transmembrane serine protease is upregulated in a variety of epithelial cancer cell lines and tumor tissues. High PRSS14/Epithin level is also implicated in the poor clinical outcome. PRSS14/Epithin plays critical roles in angiogenesis, epithelial mesenchymal transition, transendothelial migration in vitro, as well as tumor metastasis in vivo. Here, I show that immunizing antigenic peptide, SP, derived from PRSS14/Epithin sequence with adjuvants efficiently raised TH2 type antibodies in Balb/c mouse, and suppressed the lung metastasis of 4T1 breast cancer in syngenic Balb/c mouse. This inhibition is sequence specific, since srambled SP peptide sequence, Sc, failed to inhibit metastasis. Immunization of SP peptide effectively reduced lung metastasis, to a degree that was similar to PRSS14 knock down. In orthotopic tumor model with 4T1, PRSS14 knock down significantly decreases lung metastasis, and increases the survival rate of tumor bearing mice while the sites of primary tumor were mildly affected, indicating that the role of PRSS14/Epithin in metastasis rather than progression of primary tumor. No cytotoxicity was apparent for up to 6 month with alum while some effects were detected with complete freund’s adjuvant. Therefore, it was concluded, that SP is a strong candidate for safe preventive cancer metastasis vaccine.