title: hGPR87 contributes to viability of human tumor cells.
abstract: Emerging in vitro and in vivo data underline the crucial role of G-protein-coupled receptors (GPCRs) in tumorigenesis. Here, we report the contribution of hGPR87, a predicted member of the P2Y subfamily of GPCRs, to proliferation and survival of human tumor cell lines. hGPR87 mRNA transcript was found to be preferentially overexpressed in squamous cell carcinomas (SCCs) of different locations and in their lymph node metastases. Up-regulation of both, transcript and protein, was detected in samples of SCC of the lung, cervix, skin and head and neck (pharynx, larynx and epiglottis). In addition to the expression of hGPR87 in tumors which originate from stratified epithelia, we identified other hGPR87-positive tumor types including subsets of large cell and adenocarcinomas of the lung and transitional cell carcinomas of the urinary bladder. Loss of function studies using siRNA in human cancer cell lines lead to antiproliferative effects and induction of apoptosis. Like other known P2Y receptors, hGPR87 was found to be mainly located on the cell surface. The overexpression of hGPR87 preferentially in SCCs together with our functional data suggests a common molecular mechanism for SCC tumorigenesis and may provide a novel intervention site for mechanism-based antitumor therapies.
authors.affiliation: Boehringer-Ingelheim Austria GmbH, Dr. Boehringer-Gassse 5-11, Vienna, Austria.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Glatt
authors.forename: Daniel
authors.initials: D
authors.lastname: Halbauer
authors.forename: Stefan
authors.initials: S
authors.lastname: Heindl
authors.forename: Andreas
authors.initials: A
authors.lastname: Wernitznig
authors.forename: Daniela
authors.initials: D
authors.lastname: Kozina
authors.forename: Kuan-Chung
authors.initials: KC
authors.lastname: Su
authors.forename: Christina
authors.initials: C
authors.lastname: Puri
authors.forename: Pilar
authors.initials: P
authors.lastname: Garin-Chesa
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Sommergruber
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism; D017209:Apoptosis; D018287:Carcinoma, Large Cell / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002295:Carcinoma, Transitional Cell / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism; D008297:Male; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D016133:Polymerase Chain Reaction; D034741:RNA, Small Interfering / Q000378:metabolism; D049368:Receptors, Lysophosphatidic Acid / Q000378:metabolism*; D012878:Skin Neoplasms / Q000378:metabolism; D014158:Transcription, Genetic; D015854:Up-Regulation; D001749:Urinary Bladder Neoplasms / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000378:metabolism
chemical_list: C526276:GPR87 protein, human; D034741:RNA, Small Interfering; D049368:Receptors, Lysophosphatidic Acid