The transgenic expression of the β-subunit of human chorionic gonadotropin influences the growth of implanted tumor cells

Abstract

The beta subunit of human chorionic gonadotropin (βhCG) is secreted by varioustumors, and its presence associated with poor prognosis. Though exogenous hCGelicits the synthesis of molecules associated with angiogenesis, invasion, immunesuppression and chemoresistance from responsive tumor cells in vitro, the influenceof cell-extrinsic βhCG on tumorigenesis in vivo has not been adequately explored.Female C57BL/6-/-times FVBβhCG/-F1 transgenic mice demonstrated ovarian hyperplasiaand pituitary adenomas transcripts of hCG-driven, tumor-associated molecules wereheightened in the pituitary. Upon the implantation of Lewis Lung Carcinoma cells(murine lung tumor cells derived from C57BL/6 mice) in transgenic mice, tumorincidence and volume were enhanced, and increased transcription and expressionof hCG-driven, tumor-associated molecules was observed in excised tumors. Whiletreatment of these mice with Cabergoline (a potent dopamine receptor agonist)had no significant effects, ovariectomy resulted in a reduction in the lag phase,accompanied by an increase in tumor incidence and volume upon Lewis LungCarcinoma cell implantation. In tumors derived from Lewis Lung Carcinoma cellimplanted ovariectomized, transgenic mice, the transcription and expression of hCGdriven, tumor-associated molecules remained elevated and enhanced animal mortalitywas observed. Cell-extrinsic βhCG can therefore induce pro-tumorigenic effects invivo (even on tumor lineages not part of the reproductive axis), with ovarian productsmediating an ameliorating influence.