Antitumor effect of CXCR4 antagonist AMD3100 on the tumorigenic cell line of BHP10-3 papillary thyroid cancer cells

• Published in: Head & neck 2016-10, Vol.38 (10), p.1479-1486
• Main Authors: Jung, Young Ho, Lee, Doh Young, Cha, Wonjae, Kim, Bo Hae, Sung, Myung-Whun, Kim, Kwang Hyun, Ahn, Soon-Hyun
• Format: Article
• Language: English
• Subjects: AMD3100; Animals; Carcinogenesis; Carcinoma, Papillary - drug therapy; Carcinoma, Papillary - metabolism; Carcinoma, Papillary - pathology; CD24; Cell Line, Tumor; Cell Proliferation - drug effects; CXCR4; Female; Flow Cytometry; Heterocyclic Compounds - pharmacology; Heterocyclic Compounds - therapeutic use; Humans; Immunohistochemistry; Mice; Mice, Nude; papillary thyroid cancer; Receptors, CXCR4 - antagonists & inhibitors; Receptors, CXCR4 - metabolism; Thyroid Cancer, Papillary; Thyroid Neoplasms - drug therapy; Thyroid Neoplasms - metabolism; Thyroid Neoplasms - pathology; tumorigenic cell
• ISSN: 1043-3074; 1097-0347
• DOI: 10.1002/hed.24461

Background 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. Methods 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. Results 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 103 ng/mL to 105 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. Conclusion 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