剑桥大学M. P. Alcolea课题组取得一项新突破。他们的研究显示，癌前微环境重塑决定新生肿瘤的持续性。这一研究成果于2026年3月4日发表在国际顶尖学术期刊《自然》上。

在这里，该课题组研究人员发现新出现的肿瘤在它们最早期的阶段塑造了它们的微环境，这是一个决定它们生存的关键过程。对上消化道新生鳞状肿瘤的分析表明，早期肿瘤细胞的应激反应指示潜在的间质形成一个支持性的“癌前生态位”，这决定了上皮病变的长期结果。新生肿瘤下受刺激的成纤维细胞激活了伤口愈合反应，触发了潜在细胞外基质的显著重塑，导致富含纤维连接蛋白的基质支架的形成，促进肿瘤的生长。功能异型3D培养分析和体内移植实验，结合无致癌物质的健康上皮和肿瘤来源的基质，表明仅癌前生态位就足以赋予正常上皮细胞肿瘤特性。该研究组提出了一个模型，其中突变和基质对遗传应激的反应共同决定了早期肿瘤持续存在并向更高级疾病阶段发展的可能性。

据了解，突变细胞与其环境之间的相互作用在决定癌症易感性方面起着关键作用。然而，对癌前微环境如何促进早期肿瘤发生的理解仍然有限。

附：英文原文

Title: Precancerous niche remodelling dictates nascent tumour persistence

Author: Skrupskelyte, G., Rojo Arias, J. E., Ajith, H., Dang, Y., Rossetti, D., Han, S., Tang, M. K. S., Bejar, M. T., Colom, B., Fowler, J. C., Murai, K., Knight, W., Aust, D., Schmidt, M. H. H., Jszai, J., Zeki, S., Noorani, A., Jones, P. H., Rulands, S., Simons, B. D., Alcolea, M. P.

Issue&Volume: 2026-03-04

Abstract: Interactions between mutant cells and their environment have a key role in determining cancer susceptibility1,2,3. However, understanding of how the precancerous microenvironment contributes to early tumorigenesis remains limited. Here we show that newly emerging tumours at their most incipient stages shape their microenvironment in a critical process that determines their survival. Analysis of nascent squamous tumours in the upper gastrointestinal tract of the mouse reveals that the stress response of early tumour cells instructs the underlying mesenchyme to form a supportive ‘precancerous niche’, which dictates the long-term outcome of epithelial lesions. Stimulated fibroblasts beneath emerging tumours activate a wound-healing response that triggers a marked remodelling of the underlying extracellular matrix, resulting in the formation of a fibronectin-rich stromal scaffold that promotes tumour growth. Functional heterotypic 3D culture assays and in vivo grafting experiments, combining carcinogen-free healthy epithelium and tumour-derived stroma, demonstrate that the precancerous niche alone is sufficient to confer tumour properties to normal epithelial cells. We propose a model in which both mutations and the stromal response to genetic stress together define the likelihood of early tumours to persist and progress towards more advanced disease stages.

DOI: 10.1038/s41586-026-10157-8

Source: https://www.nature.com/articles/s41586-026-10157-8