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 presentin vitromodelling 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.
癌症的发生与早期肿瘤生长是受多种细胞及微环境因素影响的复杂过程。肿瘤进展的关键环节在于癌细胞与细胞外基质之间的动态相互作用——后者通过显著的结构重塑为恶性肿瘤提供支持。细胞极性丧失是肿瘤进展的早期标志，这一过程破坏正常组织结构并促进癌变转化。在此过程中，癌症相关微小RNA通过调控细胞外基质重塑、上皮-间质转化以及致瘤性血管发育等关键致癌进程，进一步驱动肿瘤生长。细胞外基质的改变（特别是硬度变化与机械转导信号）为癌细胞创造了支持性生态位，增强其存活、增殖与侵袭能力。上皮-间质转化及其亚型上皮-内皮转化通过增强肿瘤可塑性、促进癌症干细胞生成及支持肿瘤血管化参与这一进程。此外，血管生成与血管新生等血管发育过程对维持早期肿瘤生长至关重要，它们为不断演化的癌性微环境中的缺氧恶性细胞提供氧气与营养。本综述系统探讨致瘤性微环境中这些变化的核心机制，重点阐述其在肿瘤发生与早期生长中的协同作用，并深入解析当前为精准模拟早期癌症病理生理学而建立的体外模型策略。理解这些过程对于开发靶向关键促癌通路的治疗策略、改善临床预后具有至关重要的意义。
肿瘤(癌症)患者之家