HAS1high cancer associated fibroblasts located at the tumor invasion front zone promote oral squamous cell carcinoma invasion via ECM remodeling
Abstract Background Although tumor cell heterogeneity between the tumor center (TC) and invasion front (IF) of oral squamous cell carcinoma (OSCC) is well documented, the morphological, molecular, and functional characteristics of cancer-associated fibroblasts (CAFs) in these regions remain poorly u...
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BMC
2025-08-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
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| Online Access: | https://doi.org/10.1186/s13046-025-03493-6 |
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| author | Wanyong Jin Qiuya Yu Liyuan Yu Ting Zhou Xiren Wang Wanqiu Lu Xiaoxin Zhang Liang Ding Qingang Hu Yanhong Ni |
| author_facet | Wanyong Jin Qiuya Yu Liyuan Yu Ting Zhou Xiren Wang Wanqiu Lu Xiaoxin Zhang Liang Ding Qingang Hu Yanhong Ni |
| author_sort | Wanyong Jin |
| collection | DOAJ |
| description | Abstract Background Although tumor cell heterogeneity between the tumor center (TC) and invasion front (IF) of oral squamous cell carcinoma (OSCC) is well documented, the morphological, molecular, and functional characteristics of cancer-associated fibroblasts (CAFs) in these regions remain poorly understood. Methods We examined hematoxylin and eosin (H&E)–stained OSCC sections to assess CAF morphology and correlation with patient prognosis. We then isolated paired CAFs from the tumor center (CAFTC) and invasion front (CAFIF) of four OSCC patients and compared their ECM-remodeling activity and pro-tumorigenic effects on OSCC cells. Furthermore, RNA sequencing identified differentially expressed genes between CAFTC and CAFIF. Finally, based on RNA-seq findings, we knocked down hyaluronan synthase 1 (HAS1) in CAFIF to evaluate its role in extracellular matrix (ECM) remodeling and tumor invasion. Results Compared to CAFTC, CAFIF exhibited a plump cell morphology and were associated with shorter disease-free survival. Functionally, CAFIF showed higher ECM-remodeling activity and more effective ability for promoting OSCC invasion and lymph node metastasis than CAFTC. RNA-seq identified HAS1 was significantly upregulated in CAFIF, promoting hyaluronic acid (HA) production and ECM remodeling. HAS1 knockdown in CAFIF diminished ECM remodeling and attenuated the ability of CAFIF to promoting OSCC invasion. Conclusion CAFIF with plump cell morphology showed pro-invasive abilities, driven in part by HAS1 overexpression and ECM remodeling, suggesting that targeting HAS1-driven ECM remodeling could be a promising therapeutic strategy. |
| format | Article |
| id | doaj-art-f40e316caa474bdbb4acaeb3fa71bb11 |
| institution | DOAJ |
| issn | 1756-9966 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj-art-f40e316caa474bdbb4acaeb3fa71bb112025-08-20T03:06:10ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662025-08-0144111910.1186/s13046-025-03493-6HAS1high cancer associated fibroblasts located at the tumor invasion front zone promote oral squamous cell carcinoma invasion via ECM remodelingWanyong Jin0Qiuya Yu1Liyuan Yu2Ting Zhou3Xiren Wang4Wanqiu Lu5Xiaoxin Zhang6Liang Ding7Qingang Hu8Yanhong Ni9Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing UniversityCentral Laboratory of Stomatology, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing UniversityCentral Laboratory of Stomatology, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing UniversityCentral Laboratory of Stomatology, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing UniversityCentral Laboratory of Stomatology, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing UniversitySchool of Biopharmacy, China Pharmaceutical UniversityCentral Laboratory of Stomatology, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing UniversityCentral Laboratory of Stomatology, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing UniversityCentral Laboratory of Stomatology, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing UniversityCentral Laboratory of Stomatology, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing UniversityAbstract Background Although tumor cell heterogeneity between the tumor center (TC) and invasion front (IF) of oral squamous cell carcinoma (OSCC) is well documented, the morphological, molecular, and functional characteristics of cancer-associated fibroblasts (CAFs) in these regions remain poorly understood. Methods We examined hematoxylin and eosin (H&E)–stained OSCC sections to assess CAF morphology and correlation with patient prognosis. We then isolated paired CAFs from the tumor center (CAFTC) and invasion front (CAFIF) of four OSCC patients and compared their ECM-remodeling activity and pro-tumorigenic effects on OSCC cells. Furthermore, RNA sequencing identified differentially expressed genes between CAFTC and CAFIF. Finally, based on RNA-seq findings, we knocked down hyaluronan synthase 1 (HAS1) in CAFIF to evaluate its role in extracellular matrix (ECM) remodeling and tumor invasion. Results Compared to CAFTC, CAFIF exhibited a plump cell morphology and were associated with shorter disease-free survival. Functionally, CAFIF showed higher ECM-remodeling activity and more effective ability for promoting OSCC invasion and lymph node metastasis than CAFTC. RNA-seq identified HAS1 was significantly upregulated in CAFIF, promoting hyaluronic acid (HA) production and ECM remodeling. HAS1 knockdown in CAFIF diminished ECM remodeling and attenuated the ability of CAFIF to promoting OSCC invasion. Conclusion CAFIF with plump cell morphology showed pro-invasive abilities, driven in part by HAS1 overexpression and ECM remodeling, suggesting that targeting HAS1-driven ECM remodeling could be a promising therapeutic strategy.https://doi.org/10.1186/s13046-025-03493-6Oral squamous cell carcinomaCancer associated fibroblastInvasion frontExtracellular matrix remodeling |
| spellingShingle | Wanyong Jin Qiuya Yu Liyuan Yu Ting Zhou Xiren Wang Wanqiu Lu Xiaoxin Zhang Liang Ding Qingang Hu Yanhong Ni HAS1high cancer associated fibroblasts located at the tumor invasion front zone promote oral squamous cell carcinoma invasion via ECM remodeling Journal of Experimental & Clinical Cancer Research Oral squamous cell carcinoma Cancer associated fibroblast Invasion front Extracellular matrix remodeling |
| title | HAS1high cancer associated fibroblasts located at the tumor invasion front zone promote oral squamous cell carcinoma invasion via ECM remodeling |
| title_full | HAS1high cancer associated fibroblasts located at the tumor invasion front zone promote oral squamous cell carcinoma invasion via ECM remodeling |
| title_fullStr | HAS1high cancer associated fibroblasts located at the tumor invasion front zone promote oral squamous cell carcinoma invasion via ECM remodeling |
| title_full_unstemmed | HAS1high cancer associated fibroblasts located at the tumor invasion front zone promote oral squamous cell carcinoma invasion via ECM remodeling |
| title_short | HAS1high cancer associated fibroblasts located at the tumor invasion front zone promote oral squamous cell carcinoma invasion via ECM remodeling |
| title_sort | has1high cancer associated fibroblasts located at the tumor invasion front zone promote oral squamous cell carcinoma invasion via ecm remodeling |
| topic | Oral squamous cell carcinoma Cancer associated fibroblast Invasion front Extracellular matrix remodeling |
| url | https://doi.org/10.1186/s13046-025-03493-6 |
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