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

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 t...

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Autores principales: Hwang, Byeong-Oh, Park, Se-Young, Cho, Eunae Sandra, Zhang, Xianglan, Lee, Sun Kyoung, Ahn, Hyung-Joon, Chun, Kyung-Soo, Chung, Won-Yoon, Song, Na-Young
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8721674/
https://www.ncbi.nlm.nih.gov/pubmed/34987523
http://dx.doi.org/10.3389/fimmu.2021.807600
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author Hwang, Byeong-Oh
Park, Se-Young
Cho, Eunae Sandra
Zhang, Xianglan
Lee, Sun Kyoung
Ahn, Hyung-Joon
Chun, Kyung-Soo
Chung, Won-Yoon
Song, Na-Young
author_facet Hwang, Byeong-Oh
Park, Se-Young
Cho, Eunae Sandra
Zhang, Xianglan
Lee, Sun Kyoung
Ahn, Hyung-Joon
Chun, Kyung-Soo
Chung, Won-Yoon
Song, Na-Young
author_sort Hwang, Byeong-Oh
collection PubMed
description 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.
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spelling pubmed-87216742022-01-04 Platelet CLEC2-Podoplanin Axis as a Promising Target for Oral Cancer Treatment Hwang, Byeong-Oh Park, Se-Young Cho, Eunae Sandra Zhang, Xianglan Lee, Sun Kyoung Ahn, Hyung-Joon Chun, Kyung-Soo Chung, Won-Yoon Song, Na-Young Front Immunol Immunology 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. Frontiers Media S.A. 2021-12-15 /pmc/articles/PMC8721674/ /pubmed/34987523 http://dx.doi.org/10.3389/fimmu.2021.807600 Text en Copyright © 2021 Hwang, Park, Cho, Zhang, Lee, Ahn, Chun, Chung and Song https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Hwang, Byeong-Oh
Park, Se-Young
Cho, Eunae Sandra
Zhang, Xianglan
Lee, Sun Kyoung
Ahn, Hyung-Joon
Chun, Kyung-Soo
Chung, Won-Yoon
Song, Na-Young
Platelet CLEC2-Podoplanin Axis as a Promising Target for Oral Cancer Treatment
title Platelet CLEC2-Podoplanin Axis as a Promising Target for Oral Cancer Treatment
title_full Platelet CLEC2-Podoplanin Axis as a Promising Target for Oral Cancer Treatment
title_fullStr Platelet CLEC2-Podoplanin Axis as a Promising Target for Oral Cancer Treatment
title_full_unstemmed Platelet CLEC2-Podoplanin Axis as a Promising Target for Oral Cancer Treatment
title_short Platelet CLEC2-Podoplanin Axis as a Promising Target for Oral Cancer Treatment
title_sort platelet clec2-podoplanin axis as a promising target for oral cancer treatment
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8721674/
https://www.ncbi.nlm.nih.gov/pubmed/34987523
http://dx.doi.org/10.3389/fimmu.2021.807600
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