Novel leptin OB3 peptide-induced signaling and progression in thyroid cancers: Comparison with leptin

// Yu-Chen SH Yang 1, * , Yu-Tang Chin 2, * , Meng-Ti Hsieh 2, 3 , Hsuan-Yu Lai 2 , Chien-Chih Ke 4 , Dana R. Crawford 5 , Oscar K. Lee 6 , Earl Fu 7 , Shaker A. Mousa 8 , Patricia Grasso 9 , Leroy F. Liu 2 , Heng-Yu Chang 10, 11 , Heng-Yuan Tang 8 , Hung-Yun Lin 2, 3 , Paul J. Davis 8, 9 1 Joint Biobank, Office of Human Research, Taipei Medical University, Taipei, Taiwan 2 Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan 3 PhD Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan 4 Biomedical Imaging Research Center, National Yang-Ming University, Taipei, Taiwan 5 Center for Immunology and Microbial Disease, Albany Medical College, Albany, New York, USA 6 Stem Cell Research Center, National Yang-Ming University, Taipei, Taiwan 7 Department of Periodontology, School of Dentistry, National Defense Medical College, Taipei, Taiwan 8 Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, New York, USA 9 Department of Medicine, Albany Medical College, Albany, New York, USA 10 Department of Biochemistry and Molecular Cell Biology, College of Medicine, Taipei Medical University, Taipei, Taiwan 11 Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan * These authors have contributed equally to this work Correspondence to: Heng-Yu Chang, e-mail: hychang@tmu.edu.tw Hung-Yun Lin, e-mail: linhy@tmu.edu.tw Keywords: obesity, leptin, OB3-leptin peptide, cancer cell invasion Received: September 15, 2015      Accepted: March 18, 2016      Published: March 30, 2016 ABSTRACT Obesity results in increased secretion of cytokines from adipose tissue and is a risk factor for various cancers. Leptin is largely produced by adipose tissue and cancer cells. It induces cell proliferation and may serve to induce various cancers. OB3-leptin peptide (OB3) is a new class of functional leptin peptide. However, its mitogenic effect has not been determined. In the present study, because of a close link between leptin and the hypothalamic-pituitary-thyroid axis, OB3 was compared with leptin in different thyroid cancer cells for gene expression, proliferation and invasion. Neither agent stimulated cell proliferation. Leptin stimulated cell invasion, but reduced adhesion in anaplastic thyroid cancer cells. Activated ERK1/2 and STAT3 contributed to leptin-induced invasion. In contrast, OB3 did not affect expression of genes involved in proliferation and invasion. In vivo studies in the mouse showed that leptin, but not OB3, significantly increased circulating levels of thyrotropin (TSH), a growth factor for thyroid cancer. In summary, OB3 is a derivative of leptin that importantly lacks the mitogenic effects of leptin on thyroid cancer cells.