Lepucki Arkadiusz, Orlińska Kinga, Mielczarek-Palacz Aleksandra, Kabut Jacek, Olczyk Pawel, Komosińska-Vassev Katarzyna
Department of Community Pharmacy, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, 41-200 Sosnowiec, Poland.
Department of Immunology and Serology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 41-200 Sosnowiec, Poland.
J Clin Med. 2022 Feb 25;11(5):1250. doi: 10.3390/jcm11051250.
The extracellular matrix is a structure composed of many molecules, including fibrillar (types I, II, III, V, XI, XXIV, XXVII) and non-fibrillar collagens (mainly basement membrane collagens: types IV, VIII, X), non-collagenous glycoproteins (elastin, laminin, fibronectin, thrombospondin, tenascin, osteopontin, osteonectin, entactin, periostin) embedded in a gel of negatively charged water-retaining glycosaminoglycans (GAGs) such as non-sulfated hyaluronic acid (HA) and sulfated GAGs which are linked to a core protein to form proteoglycans (PGs). This highly dynamic molecular network provides critical biochemical and biomechanical cues that mediate the cell-cell and cell-matrix interactions, influence cell growth, migration and differentiation and serve as a reservoir of cytokines and growth factors' action. The breakdown of normal ECM and its replacement with tumor ECM modulate the tumor microenvironment (TME) composition and is an essential part of tumorigenesis and metastasis, acting as key driver for malignant progression. Abnormal ECM also deregulate behavior of stromal cells as well as facilitating tumor-associated angiogenesis and inflammation. Thus, the tumor matrix modulates each of the classically defined hallmarks of cancer promoting the growth, survival and invasion of the cancer. Moreover, various ECM-derived components modulate the immune response affecting T cells, tumor-associated macrophages (TAM), dendritic cells and cancer-associated fibroblasts (CAF). This review article considers the role that extracellular matrix play in breast cancer. Determining the detailed connections between the ECM and cellular processes has helped to identify novel disease markers and therapeutic targets.
细胞外基质是一种由多种分子组成的结构，包括纤维状胶原蛋白（I型、II型、III型、V型、XI型、XXIV型、XXVII型）和非纤维状胶原蛋白（主要是基底膜胶原蛋白：IV型、VIII型、X型）、非胶原蛋白糖蛋白（弹性蛋白、层粘连蛋白、纤连蛋白、血小板反应蛋白、腱生蛋白、骨桥蛋白、骨连接蛋白、巢蛋白、骨膜蛋白），它们嵌入带负电荷的保水糖胺聚糖（GAGs）凝胶中，如非硫酸化透明质酸（HA）和硫酸化GAGs，这些GAGs与核心蛋白相连形成蛋白聚糖（PGs）。这个高度动态的分子网络提供关键的生化和生物力学信号，介导细胞间和细胞与基质的相互作用，影响细胞生长、迁移和分化，并作为细胞因子和生长因子作用的储存库。正常细胞外基质的破坏及其被肿瘤细胞外基质替代，调节了肿瘤微环境（TME）的组成，是肿瘤发生和转移的重要组成部分，是恶性进展的关键驱动因素。异常的细胞外基质还会失调基质细胞的行为，促进肿瘤相关的血管生成和炎症。因此，肿瘤基质调节癌症的每一个经典定义特征，促进癌症的生长、存活和侵袭。此外，各种细胞外基质衍生成分调节免疫反应，影响T细胞、肿瘤相关巨噬细胞（TAM）、树突状细胞和癌症相关成纤维细胞（CAF）。这篇综述文章探讨了细胞外基质在乳腺癌中的作用。确定细胞外基质与细胞过程之间的详细联系有助于识别新的疾病标志物和治疗靶点。
