Integrated transcriptomic and proteomic analysis of cancer-suppressive Mesocestoides corti larvae

BACKGROUND: The larvae of Mesocestoides corti have been previously shown to abrogate the growth and metastasis of the highly aggressive B16F10 melanoma in mice. In order to investigate the potential ways in which this effect is mediated, we present, to the best of our knowledge, the most comprehensive analyses of M. corti larval molecular data so far, while listing and exploring various potentially immunomodulatory molecules found therein. We show expression and protein abundance in larvae under in vivo and in vitro conditions. A promising ortholog, M. corti Kunitz-type chymotrypsin-specific inhibitor 1 (McKI-C1) of a known cancer-suppressive Kunitz protein from Echinococcus granulosus is also tested, both in vitro and in vivo. METHODS: In order to explore the potential effector mechanisms and molecules behind its cancer-suppressive capabilities, we analyzed the M. corti larval transcriptome in the C57BL/6J and ICR mouse strains, as well as in vitro. The proteomic profiles of whole homogenate and excretory-secretory products of tetrathyridia were analyzed by nano-shotgun liquid chromatography with tandem mass spectrometry and thoroughly annotated. A Kunitz protein candidate (McKI-C1) was recombinantly expressed in Escherichia coli, biochemically characterized, and functionally tested for its anti-cancer effect with mouse melanoma B16F10 cells and mouse ovarian carcinoma ID8 cells. RESULTS: We present, to the best of our knowledge, the most extensive list of experimentally verified M. corti protein products. Many proteins potentially responsible for this tapeworm's immune-related cancer-suppressive abilities and immunomodulation were found within its proteome and transcriptome. These include numerous members of the superfamily of cysteine-rich secretory proteins, such as glioma pathogenesis-related-like proteins, and Kunitz-domain proteins. Functional tests of recombinant McKI-C1 performed both in vitro and in vivo did not confirm its expected tumor-suppressing properties. Therefore, the exact effectors of this tapeworm's likely immune-mediated anti-tumor capabilities need to be examined in further studies. CONCLUSIONS: The transcriptomic and proteomic analysis of M. corti larvae carried out in the present study produced an extensive list of promising immunomodulatory or cancer-suppressive molecules. While the molecule chosen for analysis in the present study, McKI-C1, did not show any effect in vitro or in vivo, the immunomodulatory or cancer-suppressive potential of the other experimentally verified molecules remains of interest.