Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Direct Contact with Platelets Induces Podoplanin Expression and Invasion in Human Oral Squamous Cell Carcinoma Cells

  • Park, Se-Young (Department of Applied Life Science, The Graduate School, Yonsei University) ;
  • Lee, Sun Kyoung (Department of Oral Biology, Yonsei University College of Dentistry) ;
  • Lim, Mihwa (Department of Oral Biology, Yonsei University College of Dentistry) ;
  • Kim, Bomi (Department of Oral Biology, Yonsei University College of Dentistry) ;
  • Hwang, Byeong-Oh (Department of Applied Life Science, The Graduate School, Yonsei University) ;
  • Cho, Eunae Sandra (BK21 Four Project, Yonsei University College of Dentistry) ;
  • Zhang, Xianglan (Oral Cancer Research Institute, Yonsei University College of Dentistry) ;
  • Chun, Kyung-Soo (College of Pharmacy, Keimyung University) ;
  • Chung, Won-Yoon (Department of Applied Life Science, The Graduate School, Yonsei University) ;
  • Song, Na-Young (Department of Applied Life Science, The Graduate School, Yonsei University)
  • Received : 2021.10.25
  • Accepted : 2022.01.07
  • Published : 2022.05.01
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Abstract

Oral squamous cell carcinoma (OSCC) is mostly diagnosed at an advanced stage, with local and/or distal metastasis. Thus, locoregional and/or local control of the primary tumor is crucial for a better prognosis in patients with OSCC. Platelets have long been considered major players in cancer metastasis. Traditional antiplatelet agents, such as aspirin, are thought to be potential chemotherapeutics, but they need to be used with caution because of the increased bleeding risk. Podoplanin (PDPN)-expressing cancer cells can activate platelets and promote OSCC metastasis. However, the reciprocal effect of platelets on PDPN expression in OSCC has not been investigated. In this study, we found that direct contact with platelets upregulated PDPN and integrin β1 at the protein level and promoted invasiveness of human OSCC Ca9.22 cells that express low levels of PDPN. In another human OSCC HSC3 cell line that express PDPN at an abundant level, silencing of the PDPN gene reduced cell invasiveness. Analysis of the public database further supported the co-expression of PDPN and integrin β1 and their increased expression in metastatic tissues compared to normal and tumor tissues of the oral cavity. Taken together, these data suggest that PDPN is a potential target to regulate platelet-tumor interaction and metastasis for OSCC treatment, which can overcome the limitations of traditional antiplatelet drugs.

Keywords

Acknowledgement

This study was supported by Yonsei University College of Dentistry Fund (6-2019-0022).

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