Larrea Murillo Luis, Green Megan, Mahon Niall, Saiani Alberto, Tsigkou Olga
Department of Materials, School of Natural Sciences, Faculty of Science and Engineering, The University of Manchester, Manchester M13 9PL, UK.
The Henry Royce Institute, Royce Hub Building, Manchester M13 9PL, UK.
Cancers (Basel). 2025 May 15;17(10):1675. doi: 10.3390/cancers17101675.
Cancer initiation and early tumour growth are complex processes influenced by multiple cellular and microenvironmental factors. A critical aspect of tumour progression is the dynamic interplay between cancer cells and the extracellular matrix (ECM), which undergoes significant alterations to support malignancy. The loss of cell polarity is an early hallmark of tumour progression, disrupting normal tissue architecture and fostering cancerous transformation. Circumstantially, cancer-associated microRNAs (miRNAs) regulate key oncogenic processes, including ECM remodelling, epithelial-to-mesenchymal transition (EMT), and tumorigenic vascular development, further driving tumour growth. ECM alterations, particularly changes in stiffness and mechanotransduction signals, create a supportive niche for cancer cells, enhancing their survival, proliferation, and invasion. EMT and its subtype, epithelial-to-endothelial transition (EET), contribute to tumour plasticity, promote the generation of cancer stem cells (CSCs), and support tumour vascularisation. Furthermore, processes of vascular development like vasculogenesis and angiogenesis are critical for sustaining early tumour growth, supplying oxygen and nutrients to hypoxic malignant cells within the evolving cancerous microenvironments. This review explores key mechanisms underlying these changes in tumorigenic microenvironments, with an emphasis on their collective role for tumour initiation and early tumour growth. It will further delve into present modelling strategies developed to closely mimic early cancer pathophysiology. Understanding these processes is crucial for developing targeted therapies aimed at disrupting key cancer-promoting pathways and improving clinical outcomes.
癌症起始和早期肿瘤生长是受多种细胞和微环境因素影响的复杂过程。肿瘤进展的一个关键方面是癌细胞与细胞外基质（ECM）之间的动态相互作用，细胞外基质会发生显著改变以支持恶性肿瘤的发展。细胞极性的丧失是肿瘤进展的早期标志，它破坏正常组织结构并促进癌变。此外，癌症相关的微小RNA（miRNA）调节关键的致癌过程，包括ECM重塑、上皮-间质转化（EMT）和致瘤性血管发育，进一步推动肿瘤生长。ECM的改变，特别是硬度和机械转导信号的变化，为癌细胞创造了一个支持性的微环境，提高了它们的存活、增殖和侵袭能力。EMT及其亚型上皮-内皮转化（EET）有助于肿瘤可塑性，促进癌症干细胞（CSC）的产生，并支持肿瘤血管生成。此外，血管生成和血管发生等血管发育过程对于维持早期肿瘤生长、为不断演变的癌性微环境中的缺氧恶性细胞提供氧气和营养至关重要。本综述探讨了致癌微环境中这些变化的关键机制，重点关注它们在肿瘤起始和早期肿瘤生长中的共同作用。它还将进一步深入研究为紧密模拟早期癌症病理生理学而开发的当前建模策略。了解这些过程对于开发旨在破坏关键癌症促进途径并改善临床结果的靶向治疗至关重要。
