Matrix Metalloproteinase-13 (MMP-13) Directly and Indirectly Promotes Tumor Angiogenesis

Abstract

Background:Angiogenesis is an important step in the metastatic cascade of tumors. Results: MMP-13 itself as well as VEGF-A secretion from fibroblasts promotes angiogenesis. Indeed, MMP-13 is well correlated with blood vessel density in human cancer tissues. Conclusion: MMP-13 can be a marker for prediction of malignant behaviors and a therapeutic target in cancer. Significance: This work provides new insights regarding the role of MMP-13 in tumor angiogenesis.

Multiple myeloma–derived MMP-13 mediates osteoclast fusogenesis and osteolytic disease

“…Furthermore, the ability of MMP-13 to promote OCL fusogenesis dovetailed the defects we observed in the maturation of Mmp13 -/-myeloid progenitors into multinucleated OCLs that likewise correlated with lower levels of NFATc1 and DC-STAMP expression. With regard to uncovering the MMP-13-dependent signaling cascades that underline OCL progenitor maturation, MMP-13 has been reported to activate ERK1/2 in chondrocytes as well as endothelial cells (35,59). In our studies, catalytically inactive MMP-13 similarly triggers an ERK1/2-dependent signal transduction cascade that in turn controls NFATc1 and DC-STAMP expression.…”

The progress of angiogenic factors in the development of leukemias

“…As for clinical use of MMPs and TIMPs, this must be better clarified before we use such therapeutic agents in the treatment of human AML (62). The amount of ECM molecules including type IV, V and XI collagens, laminin and aggrecan core protein will also be digested by MMPs and was related to the angiogenesis and metastasis of tumors (63), for example, MMP-1 as a negative regulatory factor in angiogenesis, growth and metastasis of tumors (64), MMP-13 promoting secretion of VEGF and inducing tumor angiogenesis in vivo (65), and important roles of stromelysin members MMP-3, MMP-10 and MMP-11 in activation of proMMPs or activation of tumor cells (66). Due to lack of a hemopexin domain, matrilysins (MMP-7 and -26) can be considered as MMPs, and it has been discovered that MMP-7 not only plays an important role in the degradation of the extracellular matrix proteins, but also plays an equally important role in protein activation, degradation, abscission and other biochemical processes of non-extracellular matrix proteins, which is essential for tumor growth and tumor angiogenesis (67).…”

Gel aloe vera reduces MMP-9 in diabetic wounds

“…During wound healing process, MMPs can clean the debris, bacteria, and broken extracellular matrix during early phase of wound healing [16]. It also has a role and affects the differentiation, migration of epithelial, angiogenesis, and apoptosis process [22]. The MMP activity was strictly regulated by the presence of tissue inhibitors of metalloproteinase (TIMP) [23].…”