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Platelet CLEC2-Podoplanin Axis as a Promising Target for Oral Cancer Treatment

Authors
 Byeong-Oh Hwang  ;  Se-Young Park  ;  Eunae Sandra Cho  ;  Xianglan Zhang  ;  Sun Kyoung Lee  ;  Hyung-Joon Ahn  ;  Kyung-Soo Chun  ;  Won-Yoon Chung  ;  Na-Young Song 
Citation
 FRONTIERS IN IMMUNOLOGY, Vol.12 : 807600, 2021-12 
Journal Title
FRONTIERS IN IMMUNOLOGY
Issue Date
2021-12
MeSH
Animals ; Antineoplastic Agents / adverse effects ; Antineoplastic Agents / therapeutic use* ; Blood Platelets / drug effects* ; Blood Platelets / metabolism ; Cell Movement / drug effects* ; Humans ; Lectins, C-Type / antagonists & inhibitors* ; Lectins, C-Type / metabolism ; Membrane Glycoproteins / antagonists & inhibitors* ; Membrane Glycoproteins / metabolism ; Molecular Targeted Therapy ; Mouth Neoplasms / blood ; Mouth Neoplasms / drug therapy* ; Mouth Neoplasms / pathology ; Neoplasm Invasiveness ; Platelet Aggregation Inhibitors / adverse effects ; Platelet Aggregation Inhibitors / therapeutic use* ; Signal Transduction ; Squamous Cell Carcinoma of Head and Neck / blood ; Squamous Cell Carcinoma of Head and Neck / drug therapy* ; Squamous Cell Carcinoma of Head and Neck / secondary ; Tumor Microenvironment
Keywords
CLEC2 ; PDPN ; ezrin/radixin/moesin (ERM) ; oral cancer ; platelets ; tumor cell-induced platelet aggregation (TCIPA)
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.
Files in This Item:
T202125135.pdf Download
DOI
10.3389/fimmu.2021.807600
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral Pathology (구강병리학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Orofacial Pain and Oral Medicine (구강내과학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Others (기타) > 1. Journal Papers
Yonsei Authors
Song, Na-Young(송나영) ORCID logo https://orcid.org/0000-0001-8658-7049
Ahn, Hyoung Joon(안형준)
Lee, Sun Kyoung(이선경) ORCID logo https://orcid.org/0000-0002-3707-8050
Zhang, Xiang Lan(장향란)
Chung, Won Yoon(정원윤) ORCID logo https://orcid.org/0000-0001-8428-9005
Cho, Eunae(조은애산드라) ORCID logo https://orcid.org/0000-0002-0820-3019
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/187699
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