小柯机器人

美国德克萨斯大学MD安德森癌症中心Raghu Kalluri团队近期取得重要工作进展，他们研究发现来自癌细胞的致癌胶原蛋白I同源三聚体与α3β1整合素结合，并影响肿瘤微生物组和免疫以促进胰腺癌。这一研究成果2022年7月21日在线发表于《癌细胞》杂志上。

与成纤维细胞产生的正常I型胶原蛋白（Col1）异源三聚体（α1/α2/α1）相比，胰腺癌细胞特异性地产生独特的Col1同源三聚体（α1/α1/α1）。Col1同源三聚体由Col1a2基因的表观遗传抑制产生，并通过癌细胞上的α3β1整合素促进致癌信号传导、癌细胞增殖、肿瘤类器官形成和生长，这与缺氧和免疫抑制肿瘤中富含厌氧拟杆菌的肿瘤微生物组相关。

Col1同源三聚体的缺失增加了胰腺导管腺癌（PDAC）小鼠的总体存活率，这与肿瘤微生物组的重新编程与增加的微嗜氧弯曲杆菌有关，这可以通过广谱抗生素逆转。Col1同源三聚体的缺失增强了T细胞浸润并使抗PD-1免疫疗法的功效成为可能。本研究确定了Col1同源三聚体对肿瘤微生物组和肿瘤免疫的功能影响，表明Col1同源三聚体-α3β1整合素信号轴是癌症特异性治疗靶点。

附：英文原文

Title: Oncogenic collagen I homotrimers from cancer cells bind to α3β1 integrin and impact tumor microbiome and immunity to promote pancreatic cancer

Author: Yang Chen, Sujuan Yang, Jena Tavormina, Desiree Tampe, Michael Zeisberg, Huamin Wang, Krishnan K. Mahadevan, Chang-Jiun Wu, Hikaru Sugimoto, Chia-Chi Chang, Robert R. Jenq, Kathleen M. McAndrews, Raghu Kalluri

Issue&Volume: 2022-07-21

Abstract: In contrast to normal type I collagen (Col1) heterotrimer (α1/α2/α1) produced by fibroblasts,pancreatic cancer cells specifically produce unique Col1 homotrimer (α1/α1/α1). Col1homotrimer results from epigenetic suppression of the Col1a2 gene and promotes oncogenic signaling, cancer cell proliferation, tumor organoidformation, and growth via α3β1 integrin on cancer cells, associated with tumor microbiomeenriched in anaerobic Bacteroidales in hypoxic and immunosuppressive tumors. Deletionof Col1 homotrimers increases overall survival of mice with pancreatic ductal adenocarcinoma(PDAC), associated with reprograming of the tumor microbiome with increased microaerophilicCampylobacterales, which can be reversed with broad-spectrum antibiotics. Deletionof Col1 homotrimers enhances T cell infiltration and enables efficacy of anti-PD-1immunotherapy. This study identifies the functional impact of Col1 homotrimers ontumor microbiome and tumor immunity, implicating Col1 homotrimer-α3β1 integrin signalingaxis as a cancer-specific therapeutic target.

DOI: 10.1016/j.ccell.2022.06.011

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(22)00275-6

Cancer Cell：《癌细胞》，创刊于2002年。隶属于细胞出版社，最新IF：38.585
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