title: Gonadotropin and tumorigenesis: Direct and indirect effects on inflammatory and immunosuppressive mediators and invasion.
abstract: Human chorionic gonadotropin (hCG), a hormone essential for pregnancy, is also ectopically expressed by a variety of cancers and is associated with poor prognosis; molecular mechanisms which may contribute to tumor progression remain ill-defined. Exogenous hCG enhanced the viability of human colorectal and lung cancer cells and promoted the growth of syngeneic tumors in mice. It induced the synthesis of VEGF, IL-8, matrix metalloprotease (MMP)-2 and MMP-9, and increased invasiveness in an MMP-dependent manner. While inducing the secretion of the tumor-associated extra-cellular matrix proteoglycan versican from tumor cells, hCG consequently caused the TLR-2-mediated generation of the inflammatory, tumor-associated cytokines TNF-α and IL-6 from peripheral blood adherent cells. The molecule up-modulated the Treg-associated transcription factor FOXP3 in tumor cells and increased the secretion of TGFβ and IL-10, thereby inhibiting T cell proliferation and inducing the differentiation FOXP3-CD4+CD25-cells into functional FOXP3+CD4+CD25+suppressor cells. Co-culture of hCG-treated tumor cells with mature bone-marrow derived dendritic cells induced the generation of active indoleamine deoxygenase. While anti-hCG antibodies restricted the growth of implanted tumor cells in nude mice, immunization of immune competent mice with a βhCG-TT conjugate supplemented with Mycobacterium indicus pranii provided synergistic survival benefit in animals implanted with syngeneic, hCG-responsive tumor cells. These studies elucidate the pathways by which hCG can promote tumorigenesis, providing further rationale for anti-hCG vaccination in the treatment of gonadotropin-sensitive tumors. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Immunoendocrinology Laboratory, National Institute of Immunology, New Delhi, India.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Khare
authors.affiliation: Immunoendocrinology Laboratory, National Institute of Immunology, New Delhi, India.
authors.forename: Anjali
authors.initials: A
authors.lastname: Bose
authors.affiliation: Immunoendocrinology Laboratory, National Institute of Immunology, New Delhi, India.
authors.forename: Poonam
authors.initials: P
authors.lastname: Singh
authors.affiliation: Immunoendocrinology Laboratory, National Institute of Immunology, New Delhi, India.
authors.forename: Sandhya
authors.initials: S
authors.lastname: Singh
authors.affiliation: Department of Biochemistry, Aligarh Muslim University, Aligarh, Uttar Pradesh, India.
authors.forename: Saleem
authors.initials: S
authors.lastname: Javed
authors.affiliation: Department of Biotechnology, Jamia Hamdard, New Delhi, India.
authors.forename: Swatantra Kumar
authors.initials: SK
authors.lastname: Jain
authors.affiliation: Immunoendocrinology Laboratory, National Institute of Immunology, New Delhi, India.
authors.forename: Om
authors.initials: O
authors.lastname: Singh
authors.affiliation: Immunoendocrinology Laboratory, National Institute of Immunology, New Delhi, India.
authors.forename: Rahul
authors.initials: R
authors.lastname: Pal
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D063646:Carcinogenesis / Q000187:drug effects / Q000276:immunology*; D045744:Cell Line, Tumor; D006063:Chorionic Gonadotropin / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D005260:Female; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000276:immunology; D018836:Inflammation Mediators / Q000276:immunology*; D016209:Interleukin-8 / Q000276:immunology; D020778:Matrix Metalloproteinase 2 / Q000276:immunology; D020780:Matrix Metalloproteinase 9 / Q000276:immunology; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000276:immunology / Q000517:prevention & control; D009369:Neoplasms / Q000276:immunology* / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D053675:Versicans / Q000276:immunology
chemical_list: D000906:Antibodies; D019496:Cancer Vaccines; D006063:Chorionic Gonadotropin; D016207:Cytokines; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D018836:Inflammation Mediators; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D053675:Versicans; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: anti-cancer vaccination; human chorionic gonadotropin; prognosis; tumor progression