The Effect Of The Echinococcus Granulosus Acute Infection On Melanoma Tumorigenesis In A Mouse Model

Background and Objective: Melanoma ranks amongst the top five cancers in both men and women. The incidence of melanoma has steadily increased over the last few decades. Echinococcus, also known as hydatid disease or hydatidosis, is a zoonotic illness, and it is highly prevalent in many areas. Occurrence of echinococcosis and cancer together is rare. It is reported that among 1200 patients with different hematologic neoplastic diseases between 1985 and 2003, only one of these individuals had concomitant acute leukemia and liver hydatidosis. It has also reported that the cancer- associated O-glycosylated Tn antigen is expressed by the cestode(EG)Echinococcus granulosus.In this study, we investigate the effect of Echinococcus infection on melanoma tumorigenesis in a mouse model. We evaluate the in vivo melanoma tumor reduction efficacy between the EG secondary infection group and post-vaccination of EG total protein group in comparison to PBS controls. A B16 mouse melanoma cell line derived from C57BL/6 mice was used for the tumor model.Methods: EG were isolated and purified aseptically from infected Xinjiang sheep's liver sample, and total protein extracted for protein vaccines. Both Kunming mice and C57BL/6 mice demonstrated secondary acute EG intraperitonial infection. ELISA, Western blot, and mouse anatomical methods were used to confirm infection. Melanoma (B16) cell line derived from C57BL/6 mice was cultured, and about 1×106 tumor cells were challenged in C57BL/6 mice at 4-5 weeks after EG infection. The in vivo tumor reduction efficacy of the post-infection and post-vaccination was evaluated. Immunohistochemical analyses were demonstrated to detect melanoma antigens in EG infected mice.Results: (1) Here we successfully demonstrated both EG infection model and melanoma murine tumor model. A certain amount of EG from sheep liver sample was infectious for both Kunming and C57BL/6 mice. (2) Five weeks after infection and after EG protein immunization of C57BL/6 mice tumors were much smaller than control groups. EG infected concomitant melanoma tumor inhibition rates was 71.22%, and EG protein immunized melanoma tumor inhibition rates was 49.16%, and statistically significan(tP1=0.024, P2=0.002, P3=0.001). (3) ELISA and Western Blot results demonstrated B16 cell total proteins have cross-reactions with EG antibodies. According to immunohistochemical analyses, cellular melanoma antibodies were detectable in infected mice sera. (4) ABC-ELISA results show that IFN-γ, TNF-βand IL-4 quantities secreted by the host system vary with the different animal group.Conclusion: We successfully established Echinococcus infection concomitant in vivo melanoma tumor C57BL/6 mice model. Accordingly, we hypothesize both EG infection and its protein immunizatin can start up anti-tumor host immune defenses.