2024年6月20日出版的《自然-遗传学》杂志发表了荷兰伊拉斯谟大学医学中心Riccardo Fodde课题组的最新研究成果。他们发现非干细胞谱系是炎症诱导肠道肿瘤发生的另一种起源。

研究人员以Paneth细胞作为模型，评估了小鼠在炎症背景下分化细胞系引发肿瘤的能力。炎症发生时，Paneth细胞特异性Apc突变会导致肠道肿瘤，这不仅让人联想到炎性肠病患者会得肿瘤，也让人联想到更大一部分的人散发性结肠癌患者。

后者可能是因为西式饮食习惯诱导炎症，而西式饮食习惯是结肠癌的主要风险因素。旨在从患者肿瘤样本中预测癌症起源的细胞机器学习方法表明：在相当一部分散发性病例中，结肠癌细胞起源于分泌细胞谱系而非干细胞。

据悉，传统观点认为，结肠癌细胞来源于干细胞。然而，先前研究表明，炎症作为结肠癌的关键风险因素会抑制肠道干细胞。

附：英文原文

Title: Non-stem cell lineages as an alternative origin of intestinal tumorigenesis in the context of inflammation

Author: Verhagen, Mathijs P., Joosten, Rosalie, Schmitt, Mark, Vlimki, Niko, Sacchetti, Andrea, Rajamki, Kristiina, Choi, Jiahn, Procopio, Paola, Silva, Sara, van der Steen, Berdine, van den Bosch, Thierry P. P., Seinstra, Danielle, de Vries, Annemarie C., Doukas, Michail, Augenlicht, Leonard H., Aaltonen, Lauri A., Fodde, Riccardo

Issue&Volume: 2024-06-20

Abstract: According to conventional views, colon cancer originates from stem cells. However, inflammation, a key risk factor for colon cancer, has been shown to suppress intestinal stemness. Here, we used Paneth cells as a model to assess the capacity of differentiated lineages to trigger tumorigenesis in the context of inflammation in mice. Upon inflammation, Paneth cell-specific Apc mutations led to intestinal tumors reminiscent not only of those arising in patients with inflammatory bowel disease, but also of a larger fraction of human sporadic colon cancers. The latter is possibly because of the inflammatory consequences of western-style dietary habits, a major colon cancer risk factor. Machine learning methods designed to predict the cell-of-origin of cancer from patient-derived tumor samples confirmed that, in a substantial fraction of sporadic cases, the origins of colon cancer reside in secretory lineages and not in stem cells.

DOI: 10.1038/s41588-024-01801-y

Source: https://www.nature.com/articles/s41588-024-01801-y