Advances in Extracellular Matrix Metalloproteinases: Implications for Renal Cell Carcinoma Pathophysiology, Diagnostics, and Therapeutics

Renal cell carcinoma (RCC) is a common tumor that heavily depends on extracellular matrix (ECM) remodeling, an essential process involved not only in normal tissue homeostasis but also in malignant growth. This article reviews the role of matrix metalloproteinases (MMPs, zinc-dependent endopeptidases) in matrix degradation and ECM reorganization in the setting of RCC. We focus on the specific role of MMP2, MMP7, and MMP9 in clear cell renal cell carcinoma (ccRCC) and major subtypes of RCC. Higher levels of these MMPs are associated with high-grade tumors, increased risk of metastasis, and poorer patient survival rates, indicating that they may have value as prognostic markers. This review also discusses how ECM composition and structure are altered in the tumor microenvironment (TME), thereby preventing cell interactions and promoting cancer growth. Finally, it compiles the existing studies to anticipate a future era in which MMPs could serve as effective prognostic biomarkers and potential treatment targets for RCC, with implications for improving diagnostic and therapeutic interventions targeting ECM remodeling to suppress cancer progression.