Immunomodulatory role of metalloproteases in cancers: Current progress and future trends

Abstract

Metalloproteinases (MPs) is a large family of proteinases with metal ions in their active centers. According to the different domains metalloproteinases can be divided into a variety of subtypes mainly including Matrix Metalloproteinases (MMPs), A Disintegrin and Metalloproteases (ADAMs) and ADAMs with Thrombospondin Motifs (ADAMTS). They have various functions such as protein hydrolysis, cell adhesion and remodeling of extracellular matrix. Metalloproteinases expressed in multiple types of cancers and participate in many pathological processes involving tumor genesis and development, invasion and metastasis by regulating signal transduction and tumor microenvironment. In this review, based on the current research progress, we summarized the structure of MPs, their expression and especially immunomodulatory role and mechanisms in cancers. Additionally, a relevant and timely update of recent advances and future directions were provided for the diagnosis and immunotherapy targeting MPs in cancers.

Subcellular localization and relevant mechanisms of human cancer‐related micropeptides

“…Mechanistically, micropeptides are able to contribute to the tumor phenotype by affecting the tumor microenvironment like blood vessels and extracellular matrix (ECM). 91 For example, lncRNA BVES-AS1 was demonstrated to encode a 50-aa-length micropeptide termed BVES-AS1-201-50aa.This micropeptide increases the expression of PCNA and MMP9 in the tumor microenvironment, thus promoting CRC cells viability, migration, and invasion. 92 However, whether one micropeptide acts via several mechanisms to affect the phenotypes of the same tumor or whether one micropeptide plays diverse roles in different tumors via more subtle and specific mechanisms should be explored further.…”

“…Thus, they have impacts on tumor phenotype, including cell proliferation, metastasis, invasion, and angiogenesis. Mechanistically, micropeptides are able to contribute to the tumor phenotype by affecting the tumor microenvironment like blood vessels and extracellular matrix (ECM) 91 . For example, lncRNA BVES‐AS1 was demonstrated to encode a 50‐aa‐length micropeptide termed BVES‐AS1‐201‐50aa.This micropeptide increases the expression of PCNA and MMP9 in the tumor microenvironment, thus promoting CRC cells viability, migration, and invasion 92 .…”

Causal associations between plasma ADAMTS-5 protein level and cancer risk: a bi-directional mendelian randomization analysis

“…ADAMTSs was particularly typical in the study of osteoarthritis, as their disintegrin domain has intercellular adhesion function, allowing them to directly adhere to the extracellular matrix and participate in regulating intracellular and extracellular signaling pathways during tumor cell invasion and migration, degrading the extracellular matrix and basement membrane [31]. Although the mechanism of ADAMTS in carcinogenesis had not been fully elucidated, recent studies had shown that differential expression of ADAMTS-1, -8, -9, and − 18 family members was associated with the occurrence and development of various tumors, including cell proliferation, migration, invasion, apoptosis, and angiogenesis [32][33][34][35].…”

A novel immune-related prognostic signature based on Chemoradiotherapy sensitivity predicts long-term survival in patients with esophageal squamous cell carcinoma

“…MMPs are produced by cancer cells, CAFs, ECs and various immune cells in the TME ( Wang et al, 2022 ). Two previous studies on microarrays found that MMPs were significantly upregulated in pCR patients, which indicated that MMPs are potential biomarkers of CRT sensitivity ( Wen et al, 2014 ; Zhang et al, 2020 ).…”

“…TME plays a key role in regulating the immune response to cancer ( De Visser & Joyce, 2023 ). Extensive remodeling of ECM often occurs during cancer progression, and ECM is degraded by the matrix metalloproteinase (MMP) family ( Wang et al, 2022 ). MMPs are produced by a variety of tissues and cells in the TME, including cancer cells, CAFs, ECs, vascular smooth muscle, macrophages, neutrophils, and lymphocytes.…”