Torre-Cea Irene, Berlana-Galán Patricia, Guerra-Paes Elena, Cáceres-Calle Daniel, Carrera-Aguado Iván, Marcos-Zazo Laura, Sánchez-Juanes Fernando, Muñoz-Félix José M
Departamento de Bioquímica y Biología Molecular, Universidad de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Spain.
Departamento de Bioquímica y Biología Molecular, Universidad de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Spain.
Matrix Biol. 2025 Feb;135:135-152. doi: 10.1016/j.matbio.2024.12.008. Epub 2024 Dec 22.
The lung is a highly vascularized tissue that often harbors metastases from various extrathoracic malignancies. Lung parenchyma consists of a complex network of alveolar epithelial cells and microvessels, structured within an architecture defined by basement membranes. Consequently, understanding the role of the extracellular matrix (ECM) in the growth of lung metastases is essential to uncover the biology of this pathology and developing targeted therapies. These basement membranes play a critical role in the progression of lung metastases, influencing multiple stages of the metastatic cascade, from the acquisition of an aggressive phenotype to intravasation, extravasation and colonization of secondary sites. This review examines the biological composition of basement membranes, focusing on their core components-collagens, fibronectin, and laminin-and their specific roles in cancer progression. Additionally, we discuss the function of integrins as primary mediators of cell adhesion and signaling between tumor cells, basement membranes and the extracellular matrix, as well as their implications for metastatic growth in the lung. We also explore vascular co-option (VCO) as a form of tumor growth resistance linked to basement membranes and tumor vasculature. Finally, the review covers current clinical therapies targeting tumor adhesion, extracellular matrix remodeling, and vascular development, aiming to improve the precision and effectiveness of treatments against lung metastases.
肺是一种血管高度丰富的组织，常存在来自各种胸外恶性肿瘤的转移灶。肺实质由肺泡上皮细胞和微血管构成的复杂网络组成，其结构由基底膜界定。因此，了解细胞外基质（ECM）在肺转移瘤生长中的作用对于揭示这种病理生物学特性和开发靶向治疗至关重要。这些基底膜在肺转移的进展中起关键作用，影响转移级联反应的多个阶段，从获得侵袭性表型到进入血管、穿出血管以及在继发部位定植。本综述探讨基底膜的生物学组成，重点关注其核心成分——胶原蛋白、纤连蛋白和层粘连蛋白——及其在癌症进展中的特定作用。此外，我们讨论整合素作为肿瘤细胞、基底膜和细胞外基质之间细胞黏附与信号传导的主要介质的功能，以及它们对肺转移瘤生长的影响。我们还探讨血管共选（VCO）作为一种与基底膜和肿瘤血管系统相关的肿瘤生长抗性形式。最后，本综述涵盖目前针对肿瘤黏附、细胞外基质重塑和血管发育的临床治疗方法，旨在提高治疗肺转移瘤的精准性和有效性。
