The transgenic expression of the β-subunit of human chorionic gonadotropin influences the growth of implanted tumor cells
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Poonam Singh1, Moumita Sarkar1, Usha Agrawal2, Ilpo Huhtaniemi3 and Rahul Pal1
1Immunoendocrinology Lab, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, INDIA-110067
2National Institute of Pathology, Safdarjang Hospital Campus, Ansari Nagar West, New Delhi, INDIA-110029
3Department of Surgery & Cancer, Imperial College London, South Kensington Campus, London, UK SW7 2AZ
Rahul Pal, email: [email protected]
Keywords: human chorionic gonadotropin; gonadotropin-associated tumorigenesis; tumor-associated genes; tumor progression; prognosis
Received: May 15, 2018 Accepted: September 10, 2018 Published: October 05, 2018
The beta subunit of human chorionic gonadotropin (βhCG) is secreted by various tumors, and its presence associated with poor prognosis. Though exogenous hCG elicits the synthesis of molecules associated with angiogenesis, invasion, immune suppression and chemoresistance from responsive tumor cells in vitro, the influence of cell-extrinsic βhCG on tumorigenesis in vivo has not been adequately explored. Female C57BL/6-/- × FVBβhCG/- F1 transgenic mice demonstrated ovarian hyperplasia and pituitary adenomas; transcripts of hCG-driven, tumor-associated molecules were heightened in the pituitary. Upon the implantation of Lewis Lung Carcinoma cells (murine lung tumor cells derived from C57BL/6 mice) in transgenic mice, tumor incidence and volume were enhanced, and increased transcription and expression of hCG-driven, tumor-associated molecules was observed in excised tumors. While treatment 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 Lung Carcinoma cell implantation. In tumors derived from Lewis Lung Carcinoma cell-implanted ovariectomized, transgenic mice, the transcription and expression of hCG-driven, tumor-associated molecules remained elevated and enhanced animal mortality was observed. Cell-extrinsic βhCG can therefore induce pro-tumorigenic effects in vivo (even on tumor lineages not part of the reproductive axis), with ovarian products mediating an ameliorating influence.
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