文章：

SEMA7A介导的并置刺激通过上调IGFBP-3在胰腺癌侵袭前沿增加IL-17RB表达

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

原文发布日期：2024-10-24

英文摘要：

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. 

摘要翻译：

肿瘤侵袭是恶性肿瘤的标志性特征。位于侵袭前沿的肿瘤细胞呈现的浸润性侵袭模式与转移及患者不良预后密切相关。然而，侵袭边缘区域调控肿瘤恶性进展的分子机制尚不明确。虽然IL-17B/IL-17RB信号通路已被证实可促进胰腺癌侵袭转移，但侵袭过程中IL-17RB上调的具体机制仍知之甚少。本研究揭示了侵袭边缘区域通过肿瘤细胞与成纤维细胞直接通讯实现IL-17RB上调的多步调控机制：肿瘤细胞ATP1A1蛋白促进SEMA7A在质膜的表达，后者通过与成纤维细胞结合诱导其分泌IGFBP-3。由此形成的IGFBP-3浓度梯度不仅影响侵袭方向，还通过增强IL-17RB表达来调控SNAI2介导的侵袭过程。这些发现凸显了局部肿瘤-成纤维细胞相互作用在促进癌细胞侵袭性中的重要性，为开发靶向这种细胞通讯的新型治疗策略提供了潜在方向。

原文链接：

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