Mesenchymal stem cell-mediated adipogenic transformation: a key driver of oral squamous cell carcinoma progression
Abstract Background Interaction between mesenchymal stem cells (MSCs) and oral squamous cell carcinoma (OSCC) cells plays a major role in OSCC progression. However, little is known about adipogenic differentiation alteration in OSCC-derived MSCs (OSCC-MSCs) and how these alterations affect OSCC grow...
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| Format: | Article |
| Language: | English |
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BMC
2025-01-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13287-025-04132-9 |
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| author | Yiting Shao Yu Du Zheng Chen Lei Xiang Shaoqin Tu Yi Feng Yuluan Hou Xiaoxing Kou Hong Ai |
| author_facet | Yiting Shao Yu Du Zheng Chen Lei Xiang Shaoqin Tu Yi Feng Yuluan Hou Xiaoxing Kou Hong Ai |
| author_sort | Yiting Shao |
| collection | DOAJ |
| description | Abstract Background Interaction between mesenchymal stem cells (MSCs) and oral squamous cell carcinoma (OSCC) cells plays a major role in OSCC progression. However, little is known about adipogenic differentiation alteration in OSCC-derived MSCs (OSCC-MSCs) and how these alterations affect OSCC growth. Methods MSCs were successfully isolated and cultured from normal gingival tissue, OSCC peritumoral tissue, and OSCC tissue. This included gingiva-derived MSCs (GMSCs), OSCC adjacent noncancerous tissues-derived MSCs (OSCCN-MSCs), and OSCC-MSCs. The adipogenic and osteogenic differentiation capabilities of these cells were evaluated using Oil Red O and Alizarin Red S staining, respectively. OSCC cells were then co-cultured with either OSCC-MSCs or GMSCs to assess the impact on OSCC cell proliferation and migration. Subcutaneous xenograft experiments were conducted in BALB/c-nu mice to further investigate the effects in vivo. Additionally, immunohistochemical staining was performed on clinical samples to determine the expression levels of fatty acid synthase (FASN) and the proliferation marker Ki67. Results OSCC-MSCs exhibited enhanced adipogenic differentiation and reduced osteogenic differentiation compared to GMSCs. OSCC-MSCs significantly increased the proliferation and migration of OSCC cells relative to GMSCs and promoted tumor growth in mouse xenografts. Lipid droplet accumulation in the stroma was significantly more pronounced in OSCC + OSCC-MSCs xenografts compared to OSCC + GMSCs xenografts. Free fatty acids (FFAs) levels were elevated in OSCC tissues compared to normal gingival tissues. Moreover, OSCC-MSCs consistently secreted higher levels of FFAs in condition medium than GMSCs. Knockdown of FASN in OSCC-MSCs reduced their adipogenic potential and inhibited their ability to promote OSCC cell proliferation and migration. Clinical sample analysis confirmed higher FASN expression in OSCC stroma, correlating with larger tumor size and increased Ki67 expression in cancer tissues, and was associated with poorer overall survival. Conclusions OSCC-MSCs promoted OSCC proliferation and migration by upregulating FASN expression and facilitating FFAs secretion. Our results provide new insight into the mechanism of OSCC progression and suggest that the FASN of OSCC-MSCs may be potential targets of OSCC in the future. |
| format | Article |
| id | doaj-art-4604f1aecc26430d9a41f1e7f6b1a68e |
| institution | Kabale University |
| issn | 1757-6512 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj-art-4604f1aecc26430d9a41f1e7f6b1a68e2025-01-26T12:18:04ZengBMCStem Cell Research & Therapy1757-65122025-01-0116111710.1186/s13287-025-04132-9Mesenchymal stem cell-mediated adipogenic transformation: a key driver of oral squamous cell carcinoma progressionYiting Shao0Yu Du1Zheng Chen2Lei Xiang3Shaoqin Tu4Yi Feng5Yuluan Hou6Xiaoxing Kou7Hong Ai8Department of Stomatology, The Third Affiliated Hospital, Sun Yat-sen UniversityDepartment of Pathology, The Third Affiliated Hospital, Sun Yat-sen UniversityDepartment of Stomatology, The Third Affiliated Hospital, Sun Yat-sen UniversityHospital of Stomatology, Guanghua School of Stomatology, South China Center of Craniofacial Stem Cell Research, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen UniversityDepartment of Stomatology, The Third Affiliated Hospital, Sun Yat-sen UniversityDepartment of Stomatology, The Third Affiliated Hospital, Sun Yat-sen UniversityDepartment of Stomatology, The Third Affiliated Hospital, Sun Yat-sen UniversityHospital of Stomatology, Guanghua School of Stomatology, South China Center of Craniofacial Stem Cell Research, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen UniversityDepartment of Stomatology, The Third Affiliated Hospital, Sun Yat-sen UniversityAbstract Background Interaction between mesenchymal stem cells (MSCs) and oral squamous cell carcinoma (OSCC) cells plays a major role in OSCC progression. However, little is known about adipogenic differentiation alteration in OSCC-derived MSCs (OSCC-MSCs) and how these alterations affect OSCC growth. Methods MSCs were successfully isolated and cultured from normal gingival tissue, OSCC peritumoral tissue, and OSCC tissue. This included gingiva-derived MSCs (GMSCs), OSCC adjacent noncancerous tissues-derived MSCs (OSCCN-MSCs), and OSCC-MSCs. The adipogenic and osteogenic differentiation capabilities of these cells were evaluated using Oil Red O and Alizarin Red S staining, respectively. OSCC cells were then co-cultured with either OSCC-MSCs or GMSCs to assess the impact on OSCC cell proliferation and migration. Subcutaneous xenograft experiments were conducted in BALB/c-nu mice to further investigate the effects in vivo. Additionally, immunohistochemical staining was performed on clinical samples to determine the expression levels of fatty acid synthase (FASN) and the proliferation marker Ki67. Results OSCC-MSCs exhibited enhanced adipogenic differentiation and reduced osteogenic differentiation compared to GMSCs. OSCC-MSCs significantly increased the proliferation and migration of OSCC cells relative to GMSCs and promoted tumor growth in mouse xenografts. Lipid droplet accumulation in the stroma was significantly more pronounced in OSCC + OSCC-MSCs xenografts compared to OSCC + GMSCs xenografts. Free fatty acids (FFAs) levels were elevated in OSCC tissues compared to normal gingival tissues. Moreover, OSCC-MSCs consistently secreted higher levels of FFAs in condition medium than GMSCs. Knockdown of FASN in OSCC-MSCs reduced their adipogenic potential and inhibited their ability to promote OSCC cell proliferation and migration. Clinical sample analysis confirmed higher FASN expression in OSCC stroma, correlating with larger tumor size and increased Ki67 expression in cancer tissues, and was associated with poorer overall survival. Conclusions OSCC-MSCs promoted OSCC proliferation and migration by upregulating FASN expression and facilitating FFAs secretion. Our results provide new insight into the mechanism of OSCC progression and suggest that the FASN of OSCC-MSCs may be potential targets of OSCC in the future.https://doi.org/10.1186/s13287-025-04132-9Adipogenic differentiationMesenchymal stem cellsTumor-derived MSCsFatty acid synthaseOral squamous cell carcinoma |
| spellingShingle | Yiting Shao Yu Du Zheng Chen Lei Xiang Shaoqin Tu Yi Feng Yuluan Hou Xiaoxing Kou Hong Ai Mesenchymal stem cell-mediated adipogenic transformation: a key driver of oral squamous cell carcinoma progression Stem Cell Research & Therapy Adipogenic differentiation Mesenchymal stem cells Tumor-derived MSCs Fatty acid synthase Oral squamous cell carcinoma |
| title | Mesenchymal stem cell-mediated adipogenic transformation: a key driver of oral squamous cell carcinoma progression |
| title_full | Mesenchymal stem cell-mediated adipogenic transformation: a key driver of oral squamous cell carcinoma progression |
| title_fullStr | Mesenchymal stem cell-mediated adipogenic transformation: a key driver of oral squamous cell carcinoma progression |
| title_full_unstemmed | Mesenchymal stem cell-mediated adipogenic transformation: a key driver of oral squamous cell carcinoma progression |
| title_short | Mesenchymal stem cell-mediated adipogenic transformation: a key driver of oral squamous cell carcinoma progression |
| title_sort | mesenchymal stem cell mediated adipogenic transformation a key driver of oral squamous cell carcinoma progression |
| topic | Adipogenic differentiation Mesenchymal stem cells Tumor-derived MSCs Fatty acid synthase Oral squamous cell carcinoma |
| url | https://doi.org/10.1186/s13287-025-04132-9 |
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