Aihua Gao, Dong Wook Kim, Meiling Pei, Ki-Yeol Kim, Young-Jin Park, Woong Nam, Hyung Jun Kim, Hyun Sil Kim, In-Ho Cha, Xianglan Zhang
{"title":"TP 阳性 CAFs 对口腔鳞状细胞癌骨质侵袭的影响","authors":"Aihua Gao, Dong Wook Kim, Meiling Pei, Ki-Yeol Kim, Young-Jin Park, Woong Nam, Hyung Jun Kim, Hyun Sil Kim, In-Ho Cha, Xianglan Zhang","doi":"10.21873/anticanres.17157","DOIUrl":null,"url":null,"abstract":"<p><strong>Background/aim: </strong>Cancer-associated fibroblasts (CAFs) have recently been suggested as critical cellular components of bone invasion in oral squamous cell carcinoma (OSCC). However, the underlying molecular mechanisms and subtypes related to their bone-invasive function are unclear. This study investigated the implications of thymidine phosphorylase (TP)-positive CAFs (TP<sup>+</sup>CAFs) in OSCC bone invasion.</p><p><strong>Materials and methods: </strong>TP expression was determined in 116 patients with OSCC using immunohistochemistry. The influence of TP expression on the biological behavior of CAFs was investigated in vitro. The possible impact of TP<sup>+</sup>CAFs on bone invasion in OSCC was further evaluated using patient-derived xenograft (PDX) mouse models.</p><p><strong>Results: </strong>In bone-invasive OSCC tissues, TP<sup>+</sup>CAFs were mainly distributed on the surface of resorbed bone tissue rather than on the tumor side. High levels of TP<sup>+</sup>CAFs were significantly associated with higher T-stage, bone invasion, and worse overall survival and recurrence-free survival in our study cohort. Recombinant human TP promoted the proliferative and invasive abilities of CAFs and increased matrix metalloproteinase-9 mRNA expression in vitro, related to bone resorption. In the PDX mouse models, TP<sup>+</sup>CAFs were found in early bone resorption on the surface of resorbed bony tissues. Bone resorption occurred more frequently in the PDX models with TP<sup>+</sup>CAFs than in those without.</p><p><strong>Conclusion: </strong>TP<sup>+</sup>CAFs were significantly associated with bone invasion and the prognosis of OSCC. This study provides insights into cellular and molecular targets for the early diagnosis and treatment of bone-invasive OSCC.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":null,"pages":null},"PeriodicalIF":1.6000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Implications of TP-positive CAFs in the Bone Invasion of Oral Squamous Cell Carcinoma.\",\"authors\":\"Aihua Gao, Dong Wook Kim, Meiling Pei, Ki-Yeol Kim, Young-Jin Park, Woong Nam, Hyung Jun Kim, Hyun Sil Kim, In-Ho Cha, Xianglan Zhang\",\"doi\":\"10.21873/anticanres.17157\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background/aim: </strong>Cancer-associated fibroblasts (CAFs) have recently been suggested as critical cellular components of bone invasion in oral squamous cell carcinoma (OSCC). However, the underlying molecular mechanisms and subtypes related to their bone-invasive function are unclear. This study investigated the implications of thymidine phosphorylase (TP)-positive CAFs (TP<sup>+</sup>CAFs) in OSCC bone invasion.</p><p><strong>Materials and methods: </strong>TP expression was determined in 116 patients with OSCC using immunohistochemistry. The influence of TP expression on the biological behavior of CAFs was investigated in vitro. The possible impact of TP<sup>+</sup>CAFs on bone invasion in OSCC was further evaluated using patient-derived xenograft (PDX) mouse models.</p><p><strong>Results: </strong>In bone-invasive OSCC tissues, TP<sup>+</sup>CAFs were mainly distributed on the surface of resorbed bone tissue rather than on the tumor side. High levels of TP<sup>+</sup>CAFs were significantly associated with higher T-stage, bone invasion, and worse overall survival and recurrence-free survival in our study cohort. Recombinant human TP promoted the proliferative and invasive abilities of CAFs and increased matrix metalloproteinase-9 mRNA expression in vitro, related to bone resorption. In the PDX mouse models, TP<sup>+</sup>CAFs were found in early bone resorption on the surface of resorbed bony tissues. Bone resorption occurred more frequently in the PDX models with TP<sup>+</sup>CAFs than in those without.</p><p><strong>Conclusion: </strong>TP<sup>+</sup>CAFs were significantly associated with bone invasion and the prognosis of OSCC. This study provides insights into cellular and molecular targets for the early diagnosis and treatment of bone-invasive OSCC.</p>\",\"PeriodicalId\":8072,\"journal\":{\"name\":\"Anticancer research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.6000,\"publicationDate\":\"2024-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Anticancer research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.21873/anticanres.17157\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Anticancer research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21873/anticanres.17157","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"ONCOLOGY","Score":null,"Total":0}
Implications of TP-positive CAFs in the Bone Invasion of Oral Squamous Cell Carcinoma.
Background/aim: Cancer-associated fibroblasts (CAFs) have recently been suggested as critical cellular components of bone invasion in oral squamous cell carcinoma (OSCC). However, the underlying molecular mechanisms and subtypes related to their bone-invasive function are unclear. This study investigated the implications of thymidine phosphorylase (TP)-positive CAFs (TP+CAFs) in OSCC bone invasion.
Materials and methods: TP expression was determined in 116 patients with OSCC using immunohistochemistry. The influence of TP expression on the biological behavior of CAFs was investigated in vitro. The possible impact of TP+CAFs on bone invasion in OSCC was further evaluated using patient-derived xenograft (PDX) mouse models.
Results: In bone-invasive OSCC tissues, TP+CAFs were mainly distributed on the surface of resorbed bone tissue rather than on the tumor side. High levels of TP+CAFs were significantly associated with higher T-stage, bone invasion, and worse overall survival and recurrence-free survival in our study cohort. Recombinant human TP promoted the proliferative and invasive abilities of CAFs and increased matrix metalloproteinase-9 mRNA expression in vitro, related to bone resorption. In the PDX mouse models, TP+CAFs were found in early bone resorption on the surface of resorbed bony tissues. Bone resorption occurred more frequently in the PDX models with TP+CAFs than in those without.
Conclusion: TP+CAFs were significantly associated with bone invasion and the prognosis of OSCC. This study provides insights into cellular and molecular targets for the early diagnosis and treatment of bone-invasive OSCC.
期刊介绍:
ANTICANCER RESEARCH is an independent international peer-reviewed journal devoted to the rapid publication of high quality original articles and reviews on all aspects of experimental and clinical oncology. Prompt evaluation of all submitted articles in confidence and rapid publication within 1-2 months of acceptance are guaranteed.
ANTICANCER RESEARCH was established in 1981 and is published monthly (bimonthly until the end of 2008). Each annual volume contains twelve issues and index. Each issue may be divided into three parts (A: Reviews, B: Experimental studies, and C: Clinical and Epidemiological studies).
Special issues, presenting the proceedings of meetings or groups of papers on topics of significant progress, will also be included in each volume. There is no limitation to the number of pages per issue.