SEMA7A-mediated juxtacrine stimulation of IGFBP-3 upregulates IL-17RB at pancreatic cancer invasive front

IF 4.8 3区 医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Yi-Ing Chen, Sui-Chih Tien, Yi-Ling Ko, Chin-Chun Chang, Min-Fen Hsu, Hung Jen Chien, Hsuan-Yu Peng, Yung-Ming Jeng, Yun-Wen Tien, Yu-Ting Chang, Ming-Chu Chang, Chun-Mei Hu
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引用次数: 0

Abstract

Tumor invasion is the hallmark of tumor malignancy. The invasive infiltration pattern of tumor cells located at the leading edge is highly correlated with metastasis and unfavorable patient outcomes. However, the regulatory mechanisms governing tumor malignancy at the invasive margin remain unclear. The IL-17B/IL-17RB pathway is known to promote pancreatic cancer invasion and metastasis, yet the specific mechanisms underlying IL-17RB upregulation during invasion are poorly understood. In this study, we unveiled a multistep process for IL-17RB upregulation at the invasive margin, which occurs through direct communication between tumor cells and fibroblasts. Tumor ATP1A1 facilitates plasma membrane expression of SEMA7A, which binds to and induces IGFBP-3 secretion from fibroblasts. The resulting gradient of IGFBP-3 influences the direction and enhances IL-17RB expression to regulate SNAI2 in invasion. These findings highlight the importance of local tumor-fibroblast interactions in promoting cancer cell invasiveness, potentially leading to the development of new therapeutic strategies targeting this communication.

Abstract Image

SEMA7A介导的IGFBP-3并体刺激可上调胰腺癌浸润前沿的IL-17RB。
肿瘤侵袭是肿瘤恶性程度的标志。位于前缘的肿瘤细胞的浸润模式与肿瘤转移和患者的不良预后高度相关。然而,侵袭边缘肿瘤恶性程度的调控机制仍不清楚。众所周知,IL-17B/IL-17RB 通路可促进胰腺癌的侵袭和转移,但人们对侵袭过程中 IL-17RB 上调的具体机制却知之甚少。在这项研究中,我们揭示了入侵边缘 IL-17RB 上调的多步骤过程,这一过程是通过肿瘤细胞和成纤维细胞之间的直接交流实现的。肿瘤 ATP1A1 促进了 SEMA7A 的质膜表达,SEMA7A 与成纤维细胞结合并诱导成纤维细胞分泌 IGFBP-3。由此产生的IGFBP-3梯度影响了IL-17RB的表达方向,并增强了IL-17RB的表达,从而调节了SNAI2的侵袭。这些发现凸显了局部肿瘤与成纤维细胞之间的相互作用在促进癌细胞侵袭性方面的重要性,从而有可能开发出针对这种交流的新治疗策略。
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来源期刊
Cancer gene therapy
Cancer gene therapy 医学-生物工程与应用微生物
CiteScore
10.20
自引率
0.00%
发文量
150
审稿时长
4-8 weeks
期刊介绍: Cancer Gene Therapy is the essential gene and cellular therapy resource for cancer researchers and clinicians, keeping readers up to date with the latest developments in gene and cellular therapies for cancer. The journal publishes original laboratory and clinical research papers, case reports and review articles. Publication topics include RNAi approaches, drug resistance, hematopoietic progenitor cell gene transfer, cancer stem cells, cellular therapies, homologous recombination, ribozyme technology, antisense technology, tumor immunotherapy and tumor suppressors, translational research, cancer therapy, gene delivery systems (viral and non-viral), anti-gene therapy (antisense, siRNA & ribozymes), apoptosis; mechanisms and therapies, vaccine development, immunology and immunotherapy, DNA synthesis and repair. Cancer Gene Therapy publishes the results of laboratory investigations, preclinical studies, and clinical trials in the field of gene transfer/gene therapy and cellular therapies as applied to cancer research. Types of articles published include original research articles; case reports; brief communications; review articles in the main fields of drug resistance/sensitivity, gene therapy, cellular therapy, tumor suppressor and anti-oncogene therapy, cytokine/tumor immunotherapy, etc.; industry perspectives; and letters to the editor.
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