研究肿瘤发生的复杂机制和检查肿瘤生态系统内肿瘤细胞的相互作用对探索有效的癌症治疗方法至关重要。动态的肿瘤生态系统不断演变，由肿瘤细胞、胞外基质(ECM)、分泌因子和肿瘤相关纤维细胞(CAF)、血管周细胞、内皮细胞(EC)、脂肪细胞和免疫细胞组成。通过合成、收缩和/或蛋白酶降解ECM成分以及释放基质保留的生长因子，ECM重塑创造了促进EC增殖、迁移和血管生成的微环境。肿瘤周围的CAF释放多种血管生成刺激物(血管生成因子、细胞因子和蛋白酶)，与ECM蛋白相互作用，从而增强前血管生成/前迁移特性并支持侵袭性肿瘤生长。靶向血管生成带来血管变化，包括减少附着连接蛋白、基底膜和血管周细胞覆盖，增加渗漏性。这有利于ECM重塑、转移定植和化疗抗性。由于更浓密和更坚硬的ECM在诱导化疗抗性方面的重要作用，直接或间接靶向ECM成分被报告为抗癌治疗的主要轴。以具体背景为基础的研究靶向血管生成和ECM的药物可能通过促进常规治疗的有效性和克服治疗抗性的障碍来减轻肿瘤负担。 ©2023美国癌症研究协会。

Studying the complex mechanisms of tumorigenesis and examining the interactions of neoplastic cells within tumor ecosystem are critical to explore the possibility of effective cancer treatment modalities. Dynamic tumor ecosystem is constantly evolving and is composed of tumor cells, extracellular matrix (ECM), secreted factors, and stromal cancer-associated fibroblasts (CAF), pericytes, endothelial cells (EC), adipocytes, and immune cells. ECM remodeling by synthesis, contraction, and/or proteolytic degradation of ECM components and release of matrix-sequestered growth factors create a microenvironment that promotes EC proliferation, migration, and angiogenesis. Stromal CAFs release multiple angiogenic cues (angiogenic growth factors, cytokines, and proteolytic enzymes) which interact with ECM proteins, thus contribute to enhance proangiogenic/promigratory properties and support aggressive tumor growth. Targeting angiogenesis brings about vascular changes including reduced adherence junction proteins, basement membrane and pericyte coverage, and increased leakiness. This facilitates ECM remodeling, metastatic colonization and chemoresistance. Owing to significant role of denser and stiffer ECM in inducing chemoresistance, direct or indirect targeting of ECM components is being reported as major axis of anticancer treatment. Exploring the agents targeting angiogenesis and ECM in a context specific manner may lead to reduced tumor burden by promoting conventional therapeutic effectiveness and overcoming the hurdles of therapy resistance.©2023 American Association for Cancer Research.