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

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.

Prognostic utility of preoperative platelet‐to‐albumin ratio in surgically treated oral cavity cancer patients

“…Additionally, platelets contribute significantly to inflammatory reactions by regulating leukocyte activity and vascular permeability 14 . Lower circulating platelet counts and the use of antiplatelet agents have been associated with more favorable prognosis for patients with head and neck cancer 13,15 . Considering that around 30% of OSCC patients suffer from malnutrition due to cancer‐related symptoms and treatments, there is a growing emphasis on nutritional assessment both before and after OSCC treatment 16 .…”

“…14 Lower circulating platelet counts and the use of antiplatelet agents have been associated with more favorable prognosis for patients with head and neck cancer. 13,15 Considering that around 30% of OSCC patients suffer from malnutrition due to cancerrelated symptoms and treatments, there is a growing emphasis on nutritional assessment both before and after OSCC treatment. 16 Serum albumin levels are commonly utilized as a marker of nutritional status, 17 and lower levels of albumin are linked to increased all-cause mortality among patients who have OSCC.…”

“…11 There is substantial evidence indicating that platelets play a significant role in tumorigenesis, cancer invasion, and distant metastasis in OSCC. 12,13 Additionally, platelets contribute significantly to inflammatory reactions by regulating leukocyte activity and vascular permeability. 14 Lower circulating platelet counts and the use of antiplatelet agents have been associated with more favorable prognosis for patients with head and neck cancer.…”

“…Due to the high availability and cost‐effectiveness, a variety of laboratory markers based on inflammation and nutrition have emerged as valuable prognostic tools in OSCC, including the well‐known neutrophil‐to‐lymphocyte ratio (NLR) 11 . There is substantial evidence indicating that platelets play a significant role in tumorigenesis, cancer invasion, and distant metastasis in OSCC 12,13 . Additionally, platelets contribute significantly to inflammatory reactions by regulating leukocyte activity and vascular permeability 14 .…”

PRF Lysates Enhance the Proliferation and Migration of Oral Squamous Carcinoma Cell Lines

“…In vitro, platelet-tumor interactions have been studied with Ca9.22 and HSC3 cells originating from OSCC [26]. We have previously implemented our established oral squamous carcinoma cell line HSC2 as a bioassay for testing the responsiveness to lysates prepared from PRF membranes, however, in the context of inflammation research [27,28].…”