Shao Yiting, Du Yu, Chen Zheng, Xiang Lei, Tu Shaoqin, Feng Yi, Hou Yuluan, Kou Xiaoxing, Ai Hong
Department of Stomatology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China.
Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China.
Stem Cell Res Ther. 2025 Jan 23;16(1):12. doi: 10.1186/s13287-025-04132-9.
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.
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.
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.
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.
间充质干细胞（MSCs）与口腔鳞状细胞癌（OSCC）细胞之间的相互作用在OSCC进展中起主要作用。然而，关于OSCC来源的MSCs（OSCC-MSCs）的成脂分化改变以及这些改变如何影响OSCC生长，人们了解甚少。
成功从正常牙龈组织、OSCC瘤周组织和OSCC组织中分离并培养MSCs。这包括牙龈来源的MSCs（GMSCs）、OSCC相邻非癌组织来源的MSCs（OSCCN-MSCs）和OSCC-MSCs。分别使用油红O和茜素红S染色评估这些细胞的成脂和成骨分化能力。然后将OSCC细胞与OSCC-MSCs或GMSCs共培养，以评估对OSCC细胞增殖和迁移的影响。在BALB/c-nu小鼠中进行皮下异种移植实验，以进一步研究体内效应。此外，对临床样本进行免疫组织化学染色，以确定脂肪酸合酶（FASN）的表达水平和增殖标志物Ki67。
与GMSCs相比，OSCC-MSCs表现出增强的成脂分化和降低的成骨分化。与GMSCs相比，OSCC-MSCs显著增加了OSCC细胞的增殖和迁移，并促进了小鼠异种移植瘤的生长。与OSCC + GMSCs异种移植瘤相比，OSCC + OSCC-MSCs异种移植瘤基质中的脂滴积累明显更明显。与正常牙龈组织相比，OSCC组织中的游离脂肪酸（FFAs）水平升高。此外，在条件培养基中，OSCC-MSCs始终比GMSCs分泌更高水平的FFAs。敲低OSCC-MSCs中的FASN可降低其成脂潜能，并抑制其促进OSCC细胞增殖和迁移的能力。临床样本分析证实，OSCC基质中FASN表达较高，与肿瘤较大、癌组织中Ki67表达增加相关，并与较差的总生存期相关。
OSCC-MSCs通过上调FASN表达和促进FFAs分泌来促进OSCC增殖和迁移。我们的结果为OSCC进展机制提供了新的见解，并表明OSCC-MSCs的FASN可能是未来OSCC的潜在靶点。
