文章：

脂肪基质细胞来源的肿瘤相关成纤维细胞通过SFRP4信号通路促进胰腺腺癌进展

Adipose Stromal Cell-Derived Cancer-Associated Fibroblasts Promote Pancreatic Adenocarcinoma Progression Through SFRP4 Signaling

原文发布日期：12 January 2026

DOI: 10.3390/cancers18020233

类型: Article

开放获取: 是

英文摘要：

Background/objectives:Progression of pancreatic ductal adenocarcinoma (PDAC) and other carcinomas relies on cancer-associated fibroblasts (CAFs). A subset of CAFs is derived from adipose stromal cells (ASCs) recruited by tumors and the ASC-CAF conversion has been associated with invasiveness and poor prognosis.Methods:To explore the underlying molecular mechanisms, we used a model based on primary ASCs derived from human visceral adipose tissue co-cultured with human PDAC cell line Capan-1. To investigate cancer progression in vivo, we also used mice orthotopically grafted with mouse KPC cells.Results:Genomic analysis revealed that Capan-1 co-culture induces Wnt and TGFβ signaling and extracellular matrix (ECM) gene expression in ASC. We investigated the function of two markers of the fibroblastic transition highly induced by cancer cells: a long non-coding RNALINC01614and a Wnt signaling modulatorSFRP4. By using ASCs with eitherSFRP4orLINC01614knocked out (ko), we showed that both genes are required for Wnt/TGFβ signaling and ECM induction in ASCs by Capan-1. Analysis of changes in Capan-1 genes that rely onLINC01614andSFRP4expression in ASCs also identified the Wnt and TGF pathways.SFRP4ko in ASCs suppressed both migration and invasion of Capan-1 cells. We show that tumors inSFRP4ko mice have less desmoplasia, less epithelial dedifferentiation, reduced growth rate, and reduced progression to metastasis.Conclusions:We conclude thatSFRP4promotes cancer progression in pancreatic cancer and is a promising therapeutic target.

摘要翻译： 

背景/目标：胰腺导管腺癌（PDAC）及其他癌种的进展依赖于癌症相关成纤维细胞（CAFs）。其中部分CAFs来源于肿瘤招募的脂肪基质细胞（ASCs），且ASC向CAF的转化与肿瘤侵袭性增强及不良预后相关。方法：为探究其分子机制，我们建立了基于人内脏脂肪组织来源的原代ASCs与人PDAC细胞系Capan-1共培养的模型。为研究体内癌症进展，我们还使用了原位移植小鼠KPC细胞的小鼠模型。结果：基因组分析显示Capan-1共培养可诱导ASC中Wnt和TGFβ信号通路及细胞外基质（ECM）基因的表达。我们研究了两个受癌细胞高度诱导的成纤维化转化标志物的功能：长链非编码RNA LINC01614和Wnt信号调节因子SFRP4。通过使用SFRP4或LINC01614基因敲除（ko）的ASCs，我们发现这两个基因均为Capan-1诱导ASC中Wnt/TGFβ信号传导及ECM生成所必需。对Capan-1细胞中依赖于ASC表达的LINC01614和SFRP4的基因变化分析同样证实了Wnt和TGF通路的关键作用。ASC中SFRP4的敲除可抑制Capan-1细胞的迁移和侵袭能力。我们在SFRP4敲除小鼠模型中观察到肿瘤纤维组织增生减少、上皮去分化程度降低、生长速度减缓以及转移进展受阻。结论：我们认为SFRP4在胰腺癌中促进癌症进展，是一个有潜力的治疗靶点。

原文链接：

Adipose Stromal Cell-Derived Cancer-Associated Fibroblasts Promote Pancreatic Adenocarcinoma Progression Through SFRP4 Signaling