Wnt5a in cancer-associated fibroblasts promotes colorectal cancer progression
Wnt5a in cancer-associated fibroblasts promotes colorectal cancer progression
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DOI：
10.1016/j.bbrc.2021.06.062
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发表时间：
2021-06-25
影响因子：
3.1
通讯作者：
Unno, Michiaki
中科院分区：
文献类型：
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作者：
Hirashima, Tomoaki;Karasawa, Hideaki;Unno, Michiaki
癌症相关成纤维细胞（CAF）是肿瘤微环境的主要组成部分，并已显示出促进癌症侵袭性。在我们之前的研究中，对来自结直肠癌（CRC）组织的成对CAFs和正常成纤维细胞的表达谱进行分析，发现与Wnt信号通路相关的基因集在结直肠CAFs中高度富集。此外，在β-连环蛋白非依赖性Wnt途径的组分中，Wnt 5a在CAFs中高度表达。由于Wnt 5a被认为是CAFs中CRC进展的调节因子，我们对171例接受CRC手术的患者进行了Wnt 5a免疫组化分析。Wnt 5a的阳性染色常见于癌间质，特别是纤维瘤区，尽管癌细胞中Wnt 5a的免疫反应性较弱。CAFs中Wnt 5a状态与肿瘤大小、浸润深度、淋巴管和血管浸润、淋巴结转移、TNM分期和复发显著相关。随后使用人重组Wnt 5a蛋白的体外分析揭示，通过用Wnt 5a刺激，癌细胞增殖和迁移显著增加。我们的研究结果表明，Wnt 5a衍生的CAFs在CRC进展中起着至关重要的作用，并有可能成为抗癌治疗的靶点。(C)2021爱思唯尔公司All rights reserved.
Cancer-associated fibroblasts (CAFs) are a major component of the tumor microenvironment and have been shown to promote cancer aggressiveness. In our previous study, analysis of expression profiles obtained from paired CAFs and normal fibroblasts from colorectal cancer (CRC) tissue revealed that gene sets related to the Wnt signaling pathway were highly enriched in colorectal CAFs. Furthermore, among the components of the beta-catenin-independent Wnt pathway, Wnt5a was highly expressed in CAFs. Since Wnt5a is considered to be a regulator of CRC progression in CAFs, we performed immunohistochemical analysis on Wnt5a in 171 patients who underwent surgery for CRC. Positive staining for Wnt5a was often found in cancer stroma, particularly in fibromatous areas, although the immunoreactivity for Wnt5a was weak in cancer cells. Wnt5a status in CAFs was significantly associated with tumor size, depth of invasion, lymphatic and vascular invasion, lymph node metastasis, TNM stage, and recurrence. Subsequent in vitro analyses using human recombinant Wnt5a protein revealed that cancer cell proliferation and migration were significantly increased by stimulation with Wnt5a. Our findings suggest that Wnt5a-derived CAFs play a crucial role in CRC progression and have potential as a target of anti-cancer therapies. (C) 2021 Elsevier Inc. All rights reserved.