Matrix Biology最新文献

{"title":"Alterations in the microenvironment of junctional epidermolysis bullosa keratinocytes: A gene expression study","authors":"Yao Wang ,&nbsp;Maria Elena Hess ,&nbsp;Yan Tan ,&nbsp;Philipp R. Esser ,&nbsp;Alexander Nyström ,&nbsp;Melanie Boerries ,&nbsp;Saliha Beyza Sayar ,&nbsp;Cristina Has","doi":"10.1016/j.matbio.2024.11.005","DOIUrl":"10.1016/j.matbio.2024.11.005","url":null,"abstract":"<div><div>Integrin α6β4 subunits and type XVII collagen are critical transmembrane proteins involved in cell-matrix adhesion in skin, while laminin 332 serves as their ligand in the basement membrane zone (BMZ). Those proteins contribute to the composition of hemidesmosomes (HDs) and pathogenic variants in their corresponding genes cause junctional epidermolysis bullosa (JEB). Although the genotype-phenotype relationships in JEB have been extensively studied, the pathogenetic changes of extracellular matrix (ECM) and cell-matrix adhesion resulting from gene mutations remain unclear. We conducted a global unbiased transcriptome analysis using bulk RNA sequencing (RNA-seq) on selected JEB donor-derived cell lines lacking integrin β4 subunit (ITGB4-), type XVII collagen (COL17-) and laminin β3 chain (LAMB3-), respectively. Additional JEB cell lines and JEB donor skin samples were used for validation of relevant findings. Collectively, the results revealed similar dysregulation patterns of ECM and focal adhesion (FAs) associated genes in ITGB4- and COL17- cell lines, while LAMB3- cells displayed a relatively opposite tendency. Importantly, key nodes in the dysregulated network were associated with ECM proteins involved in wound healing processes. Additionally, a group of inflammatory-associated genes was disclosed to be up-regulated in JEB keratinocytes and could not be normalized by the adhesion rescue. The functional assay further revealed the hierarchy of stable adhesion among mutant cell lines COL17-&gt;ITGB4-&gt;LAMB3-, which correlates with the severity of their clinical manifestations. Our results indicated a wound healing associated ECM and inflammatory microenvironment established by JEB keratinocytes.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"135 ","pages":"Pages 12-23"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using load to improve tendon/ligament tissue engineering and develop novel treatments for tendinopathy","authors":"Kenneth T. Tam ,&nbsp;Keith Baar","doi":"10.1016/j.matbio.2024.12.001","DOIUrl":"10.1016/j.matbio.2024.12.001","url":null,"abstract":"<div><div>Tendon and ligament injuries are highly prevalent but heal poorly, even with proper care. Restoration of native tissue function is complicated by the fact that these tissues vary anatomically in terms of their mechanical properties, composition, and structure. These differences develop as adaptations to diverse mechanical demands; however, pathology may alter the loads placed on the tissue. Musculoskeletal loads can be generally categorized into tension, compression, and shear. Each of these regulate distinct molecular pathways that are involved in tissue remodeling, including many of the canonical tenogenic genes. In this review, we provide a perspective on the stage-specific regulation of mechanically sensitive pathways during development and maturation of tendon and ligament tissue, including scleraxis, mohawk, and others. Furthermore, we discuss structural features of healing and diseased tendon that may contribute to aberrant loading profiles, and how the associated disturbance in molecular signaling may contribute to incomplete healing or the formation of degenerative phenotypes. The perspectives provided here draw from studies spanning <em>in vitro</em>, animal, and human experiments of healthy and diseased tendon to propose a more targeted approach to advance rehabilitation, orthobiologics, and tissue engineering.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"135 ","pages":"Pages 39-54"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cleavage of Cartilage Oligomeric Matrix Protein (COMP) by ADAMTS4 generates a neoepitope associated with osteoarthritis and other forms of degenerative joint disease","authors":"Rens de Groot ,&nbsp;Patricia Badía Folgado ,&nbsp;Kazuhiro Yamamoto ,&nbsp;Daniel R. Martin ,&nbsp;Christopher D. Koch ,&nbsp;Danielle Debruin ,&nbsp;Sophie Blagg ,&nbsp;Alexander F. Minns ,&nbsp;Sumit Bhutada ,&nbsp;Josefin Ahnström ,&nbsp;Jonathan Larkin ,&nbsp;Anders Aspberg ,&nbsp;Patrik Önnerfjord ,&nbsp;Suneel S. Apte ,&nbsp;Salvatore Santamaria","doi":"10.1016/j.matbio.2024.12.005","DOIUrl":"10.1016/j.matbio.2024.12.005","url":null,"abstract":"<div><div>Osteoarthritis (OA) is a highly prevalent joint disease, affecting millions of people worldwide and characterized by degradation of articular cartilage, subchondral bone remodeling and low-grade inflammation, leading to pain, stiffness and disability. Cartilage Oligomeric Matrix Protein (COMP) is a major structural component of cartilage and its degradation has been proposed as a marker of OA severity/progression. Several proteases cleave COMP <em>in vitro</em>, however, it is unclear which of these COMPase activities is prevalent in an osteoarthritic joint. Here, using purified recombinant proteins, we show that A Disintegrin And Metalloproteinase with Thrombospondin motifs 4 (ADAMTS4) is the most potent COMPase, followed by ADAMTS1. Using liquid chromatography-tandem mass spectrometry, we identified several novel cleavage sites in COMP resulting from ADAMTS4 and ADAMTS1 activity. Cleavage at S⁷⁷-V⁷⁸ disrupted the pentameric organization of COMP and generated a neopeptide previously identified in the synovial fluid of OA patients. Immunoblots with anti-QQS⁷⁷ antibodies confirmed that ADAMTS4 efficiently cleaved this peptide bond. By analyzing five ADAMTS4 variants, we found that the C-terminal spacer domain is strictly necessary for COMPase activity and identified the specific residues involved in the interaction with COMP. An inhibitory anti-ADAMTS4 antibody significantly decreased generation of the COMP QQS⁷⁷ neoepitope in human OA cartilage explants, implicating ADAMTS4 as a key protease in generating the QQS⁷⁷ neopeptides in OA. Since another major ADAMTS4 substrate is aggrecan, the most abundant proteoglycan in cartilage, these findings highlight that, by cleaving both COMP and aggrecan, ADAMTS4 may play a crucial role in modulating the structural integrity of cartilage.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"135 ","pages":"Pages 106-124"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional transfer of integrin co-receptor CD98hc by small extracellular vesicles improves wound healing in vivo","authors":"Floriane S. Tissot ,&nbsp;Soline Estrach ,&nbsp;Laetitia Seguin ,&nbsp;Laurence Cailleteau ,&nbsp;Ayelet Levy ,&nbsp;Daniel Aberdam ,&nbsp;Chloé C. Féral","doi":"10.1016/j.matbio.2024.12.006","DOIUrl":"10.1016/j.matbio.2024.12.006","url":null,"abstract":"<div><div>Extracellular vesicles (EVs) mediate intercellular communication. EVs are composed of a lipid bilayer and contain cytosolic proteins and RNAs. Studies highlight EVs striking functions in cell-cell crosstalk. Here, we found that small EVs can transfer functional signaling molecules through their lipid bilayer and participate in skin homeostasis. We identified a transmembrane protein CD98hc (a.k.a. SLC3A2), an integrin co-receptor (Itgb1 and Itgb3), implicated in epidermis homeostasis via its capacity in regulating extracellular matrix, as an important mediator of EV-based intercellular communication <em>in vivo</em>. We first demonstrated that healthy dermal fibroblasts produced and secreted EVs bearing characteristic of exosome-like small EVs (sEVs). We show that CD98hc, Itgb1 co-receptor, is present at the surface of sEVs, transferred and stabilized at the plasma membrane. The transferred complex is functional on recipient cells both <em>in vitro</em> and <em>in vivo</em>. Indeed, treatment with sEVs from WT, but not KO cells rescued migratory defects observed either in CD98hc KO dermal fibroblasts or in keratinocytes <em>in vitro</em>. Furthermore, injection of sEVs at the margins of wound in impaired wound healing mouse models (epidermal CD98hc KO mice exhibiting healing defect and elderly mice) improved wound closure <em>in vivo</em>. CD98hc complex transferred from sEVs remained stabilized at least 7 days after injection. Thus, our findings reveal that <em>in vivo</em> treatment with sEVs containing integrin co-receptor CD98hc could improve multiple skin afflictions.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"135 ","pages":"Pages 99-105"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A CNA-35-based high-throughput fibrosis assay reveals ORAI1 as a regulator of collagen release from pancreatic stellate cells","authors":"Rieke Schleinhege ,&nbsp;Ilka Neumann ,&nbsp;Andrea Oeckinghaus ,&nbsp;Albrecht Schwab ,&nbsp;Zoltán Pethő","doi":"10.1016/j.matbio.2024.12.004","DOIUrl":"10.1016/j.matbio.2024.12.004","url":null,"abstract":"<div><h3>Rationale</h3><div>Pancreatic stellate cells (PSCs) produce a collagen-rich connective tissue in chronic pancreatitis and pancreatic ductal adenocarcinoma (PDAC). Ca²⁺-permeable ion channels such as ORAI1 are known to affect PSC proliferation and myofibroblastic phenotype. However, it is unknown whether these channels play a role in collagen secretion.</div></div><div><h3>Methods</h3><div>Using the PSC cell line PS-1, we characterized their cell-derived matrices using staining, mass spectroscopy, and cell migration assays. We developed and validated a high-throughput <em>in vitro</em> fibrosis assay to rapidly determine collagen quantity either with Sirius Red or, in the optimized version, with the collagen-binding peptide CNA-35-tdTomato. We assessed collagen deposition upon stimulating cells with transforming growth factor β1 (TGF-β1) and/or vitamin C without or with ORAI1 modulation. Orai1 expression was assessed by immunohistochemistry in the fibrotic tumor tissue of a murine PDAC model (KPfC).</div></div><div><h3>Results</h3><div>We found that TGF-β1 and vitamin C promote collagen deposition from PSCs. We used small interfering RNA (siRNA) and the inhibitor Synta-66 to demonstrate that ORAI1 regulates collagen secretion of PSCs but not NIH-3T3 fibroblasts. Physiological levels of vitamin C induce a drastic increase of the intracellular [Ca²⁺] in PSCs, with Synta-66 inhibiting Ca²⁺ influx. Lastly, we revealed Orai1 expression in cancer-associated fibroblasts (CAFs) in murine PDAC (KPfC) samples.</div></div><div><h3>Conclusion</h3><div>In conclusion, our study introduces a robust <em>in vitro</em> assay for fibrosis and identifies ORAI1 as being engaged in PSC-driven fibrosis.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"135 ","pages":"Pages 70-86"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fibrillin-1 G234D mutation in the hybrid1 domain causes tight skin associated with dysregulated elastogenesis and increased collagen cross-linking in mice","authors":"ASM Sakhawat Hossain ,&nbsp;Maria Thea Rane Dela Cruz Clarin ,&nbsp;Kenichi Kimura ,&nbsp;George Biggin ,&nbsp;Yuki Taga ,&nbsp;Koichiro Uto ,&nbsp;Ayana Yamagishi ,&nbsp;Eri Motoyama ,&nbsp;Narenmandula ,&nbsp;Kazunori Mizuno ,&nbsp;Chikashi Nakamura ,&nbsp;Keiichi Asano ,&nbsp;Sumio Ohtsuki ,&nbsp;Tomoyuki Nakamura ,&nbsp;Sachiko Kanki ,&nbsp;Clair Baldock ,&nbsp;Erna Raja ,&nbsp;Hiromi Yanagisawa","doi":"10.1016/j.matbio.2024.11.006","DOIUrl":"10.1016/j.matbio.2024.11.006","url":null,"abstract":"<div><div>Fibrillin-1, an extracellular matrix (ECM) protein encoded by the <em>FBN1</em> gene, serves as a microfibril scaffold crucial for elastic fiber formation and homeostasis in pliable tissue such as the skin. Aside from causing Marfan syndrome, some mutations in <em>FBN1</em> result in scleroderma, marked by hardened and thicker skin which limits joint mobility. Here, we describe a tight skin phenotype in the <em>Fbn1</em>^G234D/G234D mice carrying a corresponding variant of <em>FBN1</em> in the hybrid1 domain that was identified in a patient with familial aortic dissection. Unlike scleroderma, skin thickness and collagen fiber abundance do not change in the <em>Fbn1</em>^G234D/G234D mutant skin. Instead, increased collagen cross-links were observed. In addition, short elastic fibers were sparsely located underneath the panniculus muscle layer, and an abundance of thin, aberrant elastic fibers was increased within the subcutaneous fascia, which may have tightened skin attachment to the underlying skeletal muscle. Structurally, <em>Fbn1</em>^G234D/G234D microfibrils have a disrupted shoulder region that shares similarities with hybrid1 deletion mutant microfibrils. We then demonstrate the consequence of fibrillin-1 G234D mutation on dermal fibroblast functions. Mutant primary fibroblasts produce fewer elastic fibers, exhibit slower migration and increased cell stiffness. Moreover, secretome from mutant fibroblasts are marked by enhanced secretion of ECM, ECM-modifying enzymes, proteoglycans and cytokines, which are pro-tissue repair/fibrogenic. The transcriptome of mutant fibroblasts displays an increased expression of myogenic developmental and immune-related genes. Our study proposes that imbalanced ECM homeostasis due to a fibrillin-1 G234D mutation impacts fibroblast properties with potential ramifications on skin function.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"135 ","pages":"Pages 24-38"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11747857/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anticancer effect of a single-chain variable fragment against pro-matrix metalloproteinase-7 in colon cancer","authors":"Shinhye Min ,&nbsp;Bohee Jang ,&nbsp;Ji-Hye Yun ,&nbsp;Hyeonju Yang ,&nbsp;Jee Young Sung ,&nbsp;Ga-Eun Lim ,&nbsp;Yong-Nyun Kim ,&nbsp;Weontae Lee ,&nbsp;Eok-Soo Oh","doi":"10.1016/j.matbio.2024.12.009","DOIUrl":"10.1016/j.matbio.2024.12.009","url":null,"abstract":"<div><div>Disrupting the interaction between matrix metalloproteinase-7 (MMP-7) and syndecan-2 (SDC-2) can yield anticancer effects in colon cancer cells. Here, a single-chain variable fragment (scFv) targeting the pro-domain of MMP-7 was generated as a potential candidate anticancer agent. Among the generated scFvs, those designated 1B7 and 1C3 showed the strongest abilities to inhibit the ability of MMP-7 pro-domain to directly interact with SDC-2 in vitro and decrease the cancer activities of human HT29 colon adenocarcinoma cells. Consistently, 1B7 and 1C3 inhibited the cell-surface localization of pro-MMP-7, reduced the gelatinolytic activity of MMP-7, and suppressed the cancer activities of metastatic HCT116 human colon carcinoma cells. Notably, 1B7 inhibited the primary tumor growth and lung metastasis of CT26 mouse colon cancer cells in a mouse model. Compared to 1B7, the 1B7-Fc fusion antibody showed better anti-tumorigenic activity against HCT116 cells in culture and a syngeneic mouse model. Together, these data suggest that 1B7-Fc exerts anticancer effects by interfering with the interaction of MMP-7 and SDC-2 and could be a promising therapeutic antibody for colon cancer.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"135 ","pages":"Pages 125-134"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142889269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Regulation of extracellular matrix degradation and metastatic spread by IQGAP1 through endothelin-1 receptor signalling in ovarian cancer” [Matrix Biol. 81 (2019) 17-33]","authors":"Lidia Chellini ,&nbsp;Valentina Caprara ,&nbsp;Francesca Spadaro ,&nbsp;Rosanna Sestito ,&nbsp;Anna Bagnato ,&nbsp;Laura Rosanò","doi":"10.1016/j.matbio.2024.11.003","DOIUrl":"10.1016/j.matbio.2024.11.003","url":null,"abstract":"","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"135 ","pages":"Page 161"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142734362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrins and integrin-driven secretory pathways as multi-dimensional regulators of tumor-associated macrophage recruitment and reprogramming in tumor microenvironment","authors":"Nibedita Dalpati,&nbsp;Shubham Kumar Rai,&nbsp;Prerna Sharma,&nbsp;Pranita P. Sarangi","doi":"10.1016/j.matbio.2024.12.003","DOIUrl":"10.1016/j.matbio.2024.12.003","url":null,"abstract":"<div><div>Integrins, a group of transmembrane receptors, play a crucial role in mediating the interactions between cells and extracellular matrix (ECM) proteins. The intracellular signaling initiated by these cell-matrix interactions in leukocytes mediates many essential cellular processes such as survival, migration, metabolism, and other immunological functions. Macrophages, as phagocytes, participate in both proinflammatory and anti-inflammatory processes, including progression. Numerous reports have shown that the integrin-regulated secretome, comprising cytokines, chemokines, growth factors, proteases, and other bioactive molecules, is a crucial modulator of macrophage functions in tumors, significantly influencing macrophage programming and reprogramming within the tumor microenvironment (TME) in addition to driving their step-by-step entry process into tumor tissue spaces. Importantly, studies have demonstrated a pivotal role for integrin receptor-mediated secretome and associated signaling pathways in functional reprogramming from anti-tumorigenic to pro-tumorigenic phenotype in tumor-associated macrophages (TAMs). In this comprehensive review, we have provided an in-depth analysis of the latest findings of various key pathways, mediators, and signaling cascades associated with integrin-driven polarization of macrophages in tumors. This manuscript will provide an updated understanding of the modulation of inflammatory monocytes/ macrophages and TAMs by integrin-driven secretory pathways in various functions such as migration, differentiation, and their role in tumor progression, angiogenesis, and metastasis.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"135 ","pages":"Pages 55-69"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Basement membranes in lung metastasis growth and progression","authors":"Irene Torre-Cea,&nbsp;Patricia Berlana-Galán,&nbsp;Elena Guerra-Paes,&nbsp;Daniel Cáceres-Calle,&nbsp;Iván Carrera-Aguado,&nbsp;Laura Marcos-Zazo,&nbsp;Fernando Sánchez-Juanes ,&nbsp;José M. Muñoz-Félix","doi":"10.1016/j.matbio.2024.12.008","DOIUrl":"10.1016/j.matbio.2024.12.008","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"135 ","pages":"Pages 135-152"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}