Transforming growth factor-β-regulated fractalkine as a marker of erosive bone invasion in oral squamous cell carcinoma

Seung Hwa Son, Junhee Park, Min Ju Jung, Sun Kyoung Lee, Hyungkeun Kim, Ki Rim Kim, Kwang Kyun Park, Won Yoon Chung

Research output: Contribution to journalArticlepeer-review

Abstract

Patients with oral squamous cell carcinoma (OSCC) bone invasion are surgically treated with bone resection, which results in severe physical and psychological damage. Here, we investigated the potential of fractalkine (CX3CL1), which is regulated by transforming growth factor (TGF-β), as a novel biomarker for correct prediction and early detection of OSCC-associated bone invasion. TGF-β knockdown and treatment with a TGF-β-neutralizing antibody decreased the level of fractalkine in the culture media of HSC-2 and YD10B OSCC cells. Treatment with a fractalkine-neutralizing antibody reduced TGF-β-stimulated invasion by HSC-2 and YD10B cells. Fractalkine treatment increased the viability, invasion, and uPA secretion of both OSCC cell lines. Furthermore, OSCC cell bone invasion was assessed following subcutaneous inoculation of wild-type or TGF-β knockdown OSCC cells in mouse calvaria. TGF-β knockdown prevented erosive bone invasion, reduced the number of osteoclasts at the tumor-bone interface, and downregulated fractalkine expression in mouse tumor tissues. Our results indicate that the production of fractalkine is stimulated by TGF-β and mediates TGF-β-induced cell invasion in several OSCC cell lines showing an erosive pattern of bone invasion. Fractalkine may be a useful predictive marker and therapeutic target for OSCC-induced bone destruction.

Original languageEnglish
Article numbere12750
JournalEuropean Journal of Oral Sciences
Volume129
Issue number1
DOIs
Publication statusPublished - 2021 Feb

Bibliographical note

Funding Information:
This study was supported by the Yonsei University College of Dentistry Fund (6‐2016‐0024).

Publisher Copyright:
© 2021 European Journal of Oral Sciences

All Science Journal Classification (ASJC) codes

  • Dentistry(all)

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