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The effect of antagonizing RGD-binding integrin activity in papillary thyroid cancer cell lines

Authors Cheng W, Feng F, Ma C, Wang H

Received 26 October 2015

Accepted for publication 18 January 2016

Published 11 March 2016 Volume 2016:9 Pages 1415—1423

DOI https://doi.org/10.2147/OTT.S99166

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Wei An

Peer reviewer comments 2

Editor who approved publication: Professor Daniele Santini


Weiwei Cheng, Fang Feng, Chao Ma, Hui Wang

Department of Nuclear Medicine, Shanghai Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China

Abstract: Patients with papillary thyroid cancer (PTC) generally have good prognosis, but inoperable and radioactive iodine–refractory PTC still poses significant clinical challenges due to lack of effective treatment and higher mortality rates. Given the important role of integrins in multiple steps of tumor development, integrin-targeting therapy could be an effective strategy for PTC therapy. In this study, we investigated the antitumor effect of antagonizing Arg-Gly-Asp (RGD)-binding integrin activity in several PTC cell lines. Two RGD-binding integrin heterodimers αvβ3 and αvβ5 were first determined with fluorescence-activated cell sorting (FACS) and immunofluorescence assay. Cell proliferation and apoptosis were examined by Cell Counting Kit-8 assay and FACS, respectively. Cell migration and invasion were determined by transwell assays. All three PTC cell lines examined (BCPAP, K1, and TPC1) showed a moderate-to-high expression of αvβ3 and αvβ5 (P<0.05). Antagonizing the two heterodimers with the RGD-containing antagonist showed moderate inhibitory effect on cell viability of K1 and BCPAP cells, while the inhibitory effect was more significant in TPC1 cells. Similarly, the apoptotic effect induced by antagonizing αvβ3 and αvβ5 was much stronger in TPC1 cells than in BCPAP and K1 cells. Cell migration and invasion were significantly inhibited by αvβ3 and αvβ5 antagonism in all three PTC cell lines. Our results suggested that the demonstrated expression of RGD-binding integrin on PTC cells provides the possibility of integrin-targeting treatment in PTC. The strong apoptotic effect observed in TPC1 cells indicated that a subgroup of PTC patients may benefit from the cytotoxic effect of RGD-binding integrin antagonism, while the strong inhibitory effect on migration and invasion in all three PTC cells by antagonizing αvβ3 and αvβ5 showed there is an exciting possibility that targeting RGD-binding integrin may serve a potential therapeutic approach for metastatic PTC patients.

Keywords: radioactive iodine refractory PTC, αvβ3, αvβ5, cilengitide

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