Abstract
Cancer tissues are not just simple masses of malignant cells, but rather complex and heterogeneous collections of cellular and even non-cellular components, such as endothelial cells, stromal cells, immune cells, and collagens, referred to as tumor microenvironment (TME). These multiple players in the TME develop dynamic interactions with each other, which determines the characteristics of the tumor. Platelets are the smallest cells in the bloodstream and primarily regulate blood coagulation and hemostasis. Notably, cancer patients often show thrombocytosis, a status of an increased platelet number in the bloodstream, as well as the platelet infiltration into the tumor stroma, which contributes to cancer promotion and progression. Thus, platelets function as one of the important stromal components in the TME, emerging as a promising chemotherapeutic target. However, the use of traditional antiplatelet agents, such as aspirin, has limitations mainly due to increased bleeding complications. This requires to implement new strategies to target platelets for anti-cancer effects. In oral squamous cell carcinoma (OSCC) patients, both high platelet counts and low tumor-stromal ratio (high stroma) are strongly correlated with increased metastasis and poor prognosis. OSCC tends to invade adjacent tissues and bones and spread to the lymph nodes for distant metastasis, which is a huge hurdle for OSCC treatment in spite of relatively easy access for visual examination of precancerous lesions in the oral cavity. Therefore, locoregional control of the primary tumor is crucial for OSCC treatment. Similar to thrombocytosis, higher expression of podoplanin (PDPN) has been suggested as a predictive marker for higher frequency of lymph node metastasis of OSCC. Cumulative evidence supports that platelets can directly interact with PDPN-expressing cancer cells via C-type lectin-like receptor 2 (CLEC2), contributing to cancer cell invasion and metastasis. Thus, the platelet CLEC2-PDPN axis could be a pinpoint target to inhibit interaction between platelets and OSCC, avoiding undesirable side effects. Here, we will review the role of platelets in cancer, particularly focusing on CLEC2-PDPN interaction, and will assess their potentials as therapeutic targets for OSCC treatment.
Highlights
Oral squamous cell carcinoma (OSCC) is the most prevalent type of head and neck malignancies that occur in oral cavity, salivary gland, pharynx, larynx, nasal cavity, thyroid, and bone [1]
Considering that platelets store most of the plasma transforming growth factor b (TGFb), it is plausible that platelets aggravate invasion of oral squamous cell carcinoma (OSCC), and further pre-clinical and clinical investigations will shed light on a noble would be novel strategies for OSCC treatment
Despite advances in surgical techniques and therapeutic strategies including radiotherapy and immunotherapy, the survival rate of OSCC has not been improved for the past decade due to failure of local control of primary tumor [2, 208]
Summary
Oral squamous cell carcinoma (OSCC) is the most prevalent type of head and neck malignancies that occur in oral cavity, salivary gland, pharynx, larynx, nasal cavity, thyroid, and bone [1]. In support of the tumor stroma, OSCC cells tend to invade adjacent tissues, such as bones, and spread to the lymph nodes [9] This locoregional characteristic of OSCC is the primary cause of treatment failure [10]. Instead of using traditional antiplatelet agents, the pinpoint targeting of the platelet-tumor cell interaction would be a more precise and effective strategy for OSCC treatment, avoiding undesirable harmful effects. In this regards, we will highlight the role of platelets in carcinogenesis and OSCC, focusing on the physical interaction between platelets and tumors via the CLEC2-PDPN axis
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