Biomol Ther.  2022 May;30(3):284-290. 10.4062/biomolther.2021.167.

Direct Contact with Platelets Induces Podoplanin Expression and Invasion in Human Oral Squamous Cell Carcinoma Cells

Affiliations
  • 1Department of Applied Life Science, The Graduate School, Yonsei University, Seoul 03722, Republic of Korea
  • 2BK21 Four Project, Yonsei University College of Dentistry, Seoul 03722, Republic of Korea
  • 3Department of Oral Biology, Yonsei University College of Dentistry, Seoul 03722, Republic of Korea
  • 4Department of Oral Pathology, Yonsei University College of Dentistry, Seoul 03722, Republic of Korea
  • 5Oral Cancer Research Institute, Yonsei University College of Dentistry, Seoul 03722, Republic of Korea
  • 6Department of Pathology, Yanbian University Hospital, Yanji City, Jilin Province 133000, China
  • 7College of Pharmacy, Keimyung University, Daegu 42601, Republic of Korea

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.

Keyword

Oral cancer; Platelets; Podoplanin; Direct contact; Metastasis
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