title: Parathyroid Hormone-Like Hormone is a Poor Prognosis Marker of Head and Neck Cancer and Promotes Cell Growth via RUNX2 Regulation.
abstract: Parathyroid Hormone-Like Hormone (PTHLH) is an autocrine/paracrine ligand that is up-regulated in head and neck squamous cell carcinoma (HNSCC). However, the cellular function and regulatory mechanism in HNSCC remains obscure. We investigated the clinical significance of PTHLH in HNSCC patients, and verified the role of RUNX2/PTHLH axis, which is stimulated HNSCC cell growth. In patients, PTHLH is a poor prognosis marker. PTHLH expression lead to increasing the cell proliferation potential through an autocrine/paracrine role and elevating blood calcium level in Nod-SCID mice. In public HNSCC microarray cohorts, PTHLH is found to be co-expressed with RUNX2. Physiologically, PTHLH is regulated by RUNX2 and also acting as key calcium regulator. However, elevations of calcium concentration also increased the RUNX2 expression. PTHLH, calcium, and RUNX2 form a positive feedback loop in HNSCC. Furthermore, ectopic RUNX2 expression also increased PTHLH expression and promoted proliferation potential through PTHLH expression. Using cDNA microarray analysis, we found PTHLH also stimulated expression of cell cycle regulators, namely CCNA2, CCNE2, and CDC25A in HNSCC cells, and these genes are also up-regulated in HNSCC patients. In summary, our results reveal that PTHLH expression is a poor prognosis marker in HNSCC patients, and RUNX2-PTHLH axis contributes to HNSCC tumor growth.
authors.affiliation: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.|National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan.|Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Wei-Min
authors.initials: WM
authors.lastname: Chang
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yuan-Feng
authors.initials: YF
authors.lastname: Lin
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Chia-Yi
authors.initials: CY
authors.lastname: Su
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Hsuan-Yu
authors.initials: HY
authors.lastname: Peng
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Yu-Chan
authors.initials: YC
authors.lastname: Chang
authors.affiliation: Department of Otolaryngology, Head and Neck Collaborative Oncology Group, National Cheng-Kung University, Tainan, Taiwan.
authors.forename: Jenn-Ren
authors.initials: JR
authors.lastname: Hsiao
authors.affiliation: Department of Pathology, College of Medicine, Taipei Medical University and Department of Pathology, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chi-Long
authors.initials: CL
authors.lastname: Chen
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan.|Department of Internal Medicine, National Cheng-Kung University Hospital, College of Medicine, National Cheng-Kung University, Tainan, Taiwan.
authors.forename: Jang-Yang
authors.initials: JY
authors.lastname: Chang
authors.affiliation: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.|Department of Dentistry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Yi-Shing
authors.initials: YS
authors.lastname: Shieh
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Michael
authors.initials: M
authors.lastname: Hsiao
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan.|Department of Dentistry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Shine-Gwo
authors.initials: SG
authors.lastname: Shiah
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000473:pathology; D002460:Cell Line; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006258:Head and Neck Neoplasms / Q000175:diagnosis* / Q000473:pathology; D006801:Humans; D016513:Mice, SCID; D046228:Microarray Analysis; D023421:Models, Animal; D044162:Parathyroid Hormone-Related Protein / Q000378:metabolism*; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D050659:Core Binding Factor Alpha 1 Subunit; C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein; C493709:RUNX2 protein, human