title: Antitumor effect of CXCR4 antagonist AMD3100 on the tumorigenic cell line of BHP10-3 papillary thyroid cancer cells.
abstract: A tumorigenic cell line (BHP10-3M) derived from nontumorigenic papillary thyroid carcinoma (PTC) cells (BHP10-3) having rearranged during transfection (RET)/PTC1 gene rearrangement might have a higher expression of CXCR4, either quantitatively or functionally. The authors also postulated that CXCR4-mediated invasion or tumorigenesis could be blocked by CXCR4 antagonists, including AMD3100.
  
  
  
  The expression of CXCR4 in BHP10-3 and BHP10-3M cells was assessed using immunoblot analysis, flow cytometry, and quantitative reverse-transcriptase polymerase chain reaction (RT-PCR). The effect of AMD3100 on BHP10-3 and BHP10-3M cell lines was evaluated using cell proliferation assay, invasion assay, and tumor growth experiment in nude mice.
  
  
  
  Immunoblotting, flow cytometry, and quantitative RT-PCR proved that BHP10-3M cells expressed a higher level of CXCR4 than BHP10-3 cells. Although blocking CXCR4 with AMD3100 did not suppress cell proliferation in both cell lines from 1 ng/mL to 100 ng/mL concentration, AMD3100 suppressed invasion of BHP10-3M cells in vitro in a dose-dependent manner. At higher concentrations from 10(3) ng/mL to 10(5) ng/mL, the proliferation of BHP10-3M cells was inhibited more strongly by AMD3100 than that of BHP10-3 cells. Intraperitoneal injection of AMD3100 inhibited tumor formation by BHP10-3M cells in the thyroid of nude mice.
  
  
  
  A tumorigenic cell line (BHP10-3M) of PTC showed higher expression of CXCR4 quantitatively and functionally than a nontumorigenic cell line (BHP10-3). The CXCR4 antagonist (AMD3100) showed a significant antitumor effect on the tumorigenic cell line of PTC BHP10-3 cells both in vitro and in vivo. CXCR4 antagonist can be expected to have an adjuvant role in the management of PTC. © 2016 Wiley Periodicals, Inc. Head Neck, 2016 © 2016 Wiley Periodicals, Inc. Head Neck 38: First-1486, 2016.
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery, Seoul National University Boramae Hospital, Seoul, South Korea.
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Jung
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery, Seoul National University Boramae Hospital, Seoul, South Korea.
authors.forename: Doh Young
authors.initials: DY
authors.lastname: Lee
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery, Seoul National University Boramae Hospital, Seoul, South Korea.
authors.forename: Wonjae
authors.initials: W
authors.lastname: Cha
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery, Seoul National University Boramae Hospital, Seoul, South Korea.
authors.forename: Bo Hae
authors.initials: BH
authors.lastname: Kim
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Myung-Whun
authors.initials: MW
authors.lastname: Sung
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery, Seoul National University Boramae Hospital, Seoul, South Korea.
authors.forename: Kwang Hyun
authors.initials: KH
authors.lastname: Kim
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery, Seoul National University Bundang Hospital, Seongnam, South Korea. ahnsh30@snu.ac.kr.
authors.forename: Soon-Hyun
authors.initials: SH
authors.lastname: Ahn
mesh_terms: D000818:Animals; D001596:Benzylamines; D063646:Carcinogenesis; D002291:Carcinoma, Papillary / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000080027:Cyclams; D005260:Female; D005434:Flow Cytometry; D006571:Heterocyclic Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D001596:Benzylamines; C527276:CXCR4 protein, human; D000080027:Cyclams; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; C088327:plerixafor
keywords: AMD3100; CD24; CXCR4; papillary thyroid cancer; tumorigenic cell