The angiostatic molecule Multimerin 2 is processed by MMP-9 to allow sprouting angiogenesis

Andreuzzi, Eva; Colladel, Roberta; Pellicani, Rosanna; Tarticchio, Giulia; Cannizzaro, Renato; Spessotto, Paola; Bussolati, Benedetta; Brossa, Alessia; Paoli, Paolo De; Canzonieri, Vincenzo; Iozzo, Renato V.; Colombatti, Alfonso; Mongiat, Maurizio

doi:10.1016/j.matbio.2017.04.002

Cited by 62 publications

(52 citation statements)

References 62 publications

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“…CCN3 is pro-angiogenic, while CCN5 is anti-angiogenic [47,48,49,50]. Multimerin 2 (MMRN2) has anti-angiogenesis effects, and its down-modulation occurs in the context of tumor-associated angiogenesis [51,52]. …”

Section: Angiogenesis Mechanism In Cancermentioning

confidence: 99%

The Role of Angiogenesis in Cancer Treatment

2017

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A number of anti-angiogenesis drugs have been FDA-approved and are being used in cancer treatment, and a number of other agents are in different stages of clinical development or in preclinical evaluation. However, pharmacologic anti-angiogenesis strategies that arrest tumor progression might not be enough to eradicate tumors. Decreased anti-angiogenesis activity in single mechanism-based anti-angiogenic strategies is due to the redundancy, multiplicity, and development of compensatory mechanism by which blood vessels are remodeled. Improving anti-angiogenesis drug efficacy will require identification of broad-spectrum anti-angiogenesis targets. These strategies may have novel features, such as increased porosity, and are the result of complex interactions among endothelial cells, extracellular matrix proteins, growth factors, pericyte, and smooth muscle cells. Thus, combinations of anti-angiogenic drugs and other anticancer strategies such as chemotherapy appear essential for optimal outcome in cancer patients. This review will focus on the role of anti-angiogenesis strategies in cancer treatment.

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Section: Angiogenesis Mechanism In Cancermentioning

confidence: 99%

The Role of Angiogenesis in Cancer Treatment

2017

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“…Degradation of angiostatic factors is another mechanism with which MMPs promote angiogenesis. For instance, MMP‐9 has been shown to be involved in the degradation of multimerin 2, an ECM molecule with angiostatic functions (Andreuzzi et al, ). Multimerin 2 is an ECM glycoprotein that can interfere with VEGF‐A signaling through VEGFR2 and as such, acts as an angiostatic factor (Lorenzon et al, ).…”

Section: Functional Roles Of Mmps and Adams In The Tumor Microenvironmentioning

confidence: 99%

Metalloproteinases and their roles in human cancer

Roy

Morad

Jedinak

et al. 2019

The Anatomical Record

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It is now widely appreciated that members of the matrix metalloproteinase (MMP) family of enzymes play a key role in cancer development and progression along with many of the hallmarks associated with them. The activity of these enzymes has been directly implicated in extracellular matrix remodeling, the processing of growth factors and receptors, the modulation of cell migration, proliferation, and invasion, the epithelial to mesenchymal transition, the regulation of immune responses, and the control of angiogenesis. Certain MMP family members have been validated as biomarkers of a variety of human cancers including those of the breast, brain, pancreas, prostate, ovary, and others. The related metalloproteinases, the A disintegrin and metalloproteinases (ADAMs), share a number of these functions as well. Here, we explore these essential metalloproteinases and some of their disease-associated activities in detail as well as some of their complementary translational potential. Anat Rec, 303:1557-1572, 2020.Matrix metalloproteinases (MMPs) are a multigene family of metal-dependent endopeptidases that play important and diverse roles in normal physiological and pathological processes. The classic domain structure of MMP family members can be found in Figure 1 (Roy et al., 2009). MMPs include an amino-terminal signal peptide required for secretion, a pro-domain that mediates latency via a cysteine-switch mechanism and a Zn 2+ -dependent catalytic domain that is responsible for enzymatic function. A majority of MMPs also contain a C-terminal hemopexinlike domain that provides substrate specificity. MMP activity is the rate-limiting step in extracellular matrix (ECM) degradation and it can regulate the activity of other proteases, growth factors, cytokines, and cell-surface ligands

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“…MMRN2 has been shown to be a substrate for MMP9, although it is unclear whether the subsequent cleaved fragments can still bind to members of the CTLD group 14 family and clearly warrants further investigation [216]. Intriguingly, as mentioned previously, CD248 overexpression results in upregulation of MMP9 posing a scenario in which MMRN2 could be processed by MMP9 potentially regulating CD248-MMRN2 binding.…”

Section: Considerations and Perspectivesmentioning

confidence: 89%

C‐type lectin domain group 14 proteins in vascular biology, cancer and inflammation

et al. 2019

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The C‐type lectin domain (CTLD) group 14 family of transmembrane glycoproteins consist of thrombomodulin, CD93, CLEC14A and CD248 (endosialin or tumour endothelial marker‐1). These cell surface proteins exhibit similar ectodomain architecture and yet mediate a diverse range of cellular functions, including but not restricted to angiogenesis, inflammation and cell adhesion. Thrombomodulin, CD93 and CLEC14A can be expressed by endothelial cells, whereas CD248 is expressed by vasculature associated pericytes, activated fibroblasts and tumour cells among other cell types. In this article, we review the current literature of these family members including their expression profiles, interacting partners, as well as established and speculated functions. We focus primarily on their roles in the vasculature and inflammation as well as their contributions to tumour immunology. The CTLD group 14 family shares several characteristic features including their ability to be proteolytically cleaved and engagement of some shared extracellular matrix ligands. Each family member has strong links to tumour development and in particular CD93, CLEC14A and CD248 have been proposed as attractive candidate targets for cancer therapy.

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The angiostatic molecule Multimerin 2 is processed by MMP-9 to allow sprouting angiogenesis

Cited by 62 publications

References 62 publications

The Role of Angiogenesis in Cancer Treatment

The Role of Angiogenesis in Cancer Treatment

Metalloproteinases and their roles in human cancer

C‐type lectin domain group 14 proteins in vascular biology, cancer and inflammation

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