Matrix Effectors in the Pathogenesis of Keratinocyte-Derived Carcinomas

Frontiers in Medicine

Carolina Constantin²  Adriana Munteanu²  Monica Neagu²  Aristidis Tsatsakis³  Mihaela Surcel⁴  George N. Tzanakakis⁵  Rafaela-Maria Kavasi⁵  Dragana Nikitovic⁵ 

[1] Colentina Hospital, Bucharest, Romania;Doctoral School, University of Bucharest, Bucharest, Romania;Forensic Science Department, Medical School, University of Crete, Heraklion, Greece;Immunology Laboratory, Victor Babes National Institute of Pathology, Bucharest, Romania;Laboratory of Histology-Embryology, Medical School, University of Crete, Heraklion, Greece;

关键词: extracellular matrix;    hyaluronan;    collagen;    proteoglycans;    metalloproteinases;    skin;   

DOI  :  10.3389/fmed.2022.879500

来源: DOAJ

【 摘 要 】

Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), referred to as keratinocyte carcinomas, are skin cancer with the highest incidence. BCCs, rarely metastasize; whereas, though generally not characterized by high lethality, approximately 2–4% of primary cSCCs metastasize with patients exhibiting poor prognosis. The extracellular matrix (ECM) serves as a scaffold that provides structural and biological support to cells in all human tissues. The main components of the ECM, including fibrillar proteins, proteoglycans (PGs), glycosaminoglycans (GAGs), and adhesion proteins such as fibronectin, are secreted by the cells in a tissue-specific manner, critical for the proper function of each organ. The skin compartmentalization to the epidermis and dermis compartments is based on a basement membrane (BM), a highly specialized network of ECM proteins that separate and unify the two compartments. The stiffness and assembly of BM and tensile forces affect tumor progenitors' invasion at the stratified epithelium's stromal border. Likewise, the mechanical properties of the stroma, e.g., stiffness, are directly correlated to the pathogenesis of the keratinocyte carcinomas. Since the ECM is a pool for various growth factors, cytokines, and chemokines, its' intense remodeling in the aberrant cancer tissue milieu affects biological functions, such as angiogenesis, adhesion, proliferation, or cell motility by regulating specific signaling pathways. This review discusses the structural and functional modulations of the keratinocyte carcinoma microenvironment. Furthermore, we debate how ECM remodeling affects the pathogenesis of these skin cancers.

【 授权许可】

Unknown