We previously showed that upregulation of adipocyte enhancer-binding protein 1 (AEBP1) in vascular endothelial cells promotes tumor angiogenesis. In the present study, we aimed to clarify the role of stromalAEBP1/ACLP expression in oral squamous cell carcinoma (OSCC). Immunohistochemical analysis showed that ACLP is abundantly expressed in cancer-associated fibroblasts (CAFs) in primary OSCC tissues and that upregulated expression of ACLP is associated with disease progression. Analysis using CAFs obtained from surgically resected OSCCs showed that the expression ofAEBP1/ACLP in CAFs is upregulated by co-culture with OSCC cells or treatment with TGF-β1, suggesting cancer-cell-derived TGF-β1 inducesAEBP1/ACLP in CAFs. Collagen gel contraction assays showed that ACLP contributes to the activation of CAFs. In addition, CAF-derived ACLP promotes migration, invasion, and in vivo tumor formation by OSCC cells. Notably, tumor stromal ACLP expression correlated positively with collagen expression and correlated inversely with CD8+ T cell infiltration into primary OSCC tumors. Boyden chamber assays suggested that ACLP in CAFs may attenuate CD8+ T cell migration. Our results suggest that stromal ACLP contributes to the development of OSCCs, and that ACLP is a potential therapeutic target.
我们既往研究表明，血管内皮细胞中脂肪细胞增强子结合蛋白1（AEBP1）的上调可促进肿瘤血管生成。本研究旨在阐明间质AEBP1/ACLP在口腔鳞状细胞癌（OSCC）中的作用机制。免疫组化分析显示，ACLP在原发性OSCC组织的癌相关成纤维细胞（CAFs）中高表达，且其表达上调与疾病进展相关。通过对手术切除OSCC标本中获取的CAFs进行分析发现，与OSCC细胞共培养或经TGF-β1处理后，CAFs中AEBP1/ACLP表达显著上调，提示癌细胞来源的TGF-β1可诱导CAFs中AEBP1/ACLP表达。胶原凝胶收缩实验证实ACLP参与CAFs的活化过程。此外，CAFs来源的ACLP可促进OSCC细胞的迁移、侵袭及体内成瘤能力。值得注意的是，肿瘤间质ACLP表达与胶原表达呈正相关，而与原发性OSCC肿瘤中CD8+ T细胞浸润呈负相关。Boyden小室迁移实验提示CAFs中的ACLP可能抑制CD8+ T细胞迁移。本研究结果表明间质ACLP参与OSCC的发生发展过程，ACLP可能成为潜在的治疗靶点。
肿瘤(癌症)患者之家