Cell-surface association between matrix metalloproteinases and integrins: role of the complexes in leukocyte migration and cancer progression

Abstract

Leukocyte motility is known to be dependent on both ␤2-integrins and matrix metalloproteinases MMP-2/-9 or gelatinases, which mediate leukocyte adhesion and the proteolysis needed for invasion, respectively. Gelatinases not only play an important role in cell migration, tissue remodeling, and angiogenesis during development, but are also involved in the progression and invasiveness of many cancers, including leukemias. The concept that MMPs associate with integrins, as well as their importance in some physiologic and pathologic conditions, has been advanced previously but has not been examined on leukocytes. This review will examine mainly the function of the MMP-integrin complexes in normal leukocyte migration and the effect of integrin and broad-spectrum MMP inhibitors in tumor

Endosialin (Tem1) Is a Marker of Tumor-Associated Myofibroblasts and Tumor Vessel-Associated Mural Cells

“…The promigratory and proinvasive phenotype of tumors grown in wild-type mice compared to endosialin-null mice also suggests a role of endosialin in cell migration and/or matrix remodeling. 21 Our cellular loss-of-function experiments showed no differences in matrix metalloproteinase secretion but a strong effect on cell migration and proliferation. Factors and microenvironmental conditions regulating endosialin expression have not yet been defined.…”

Normalization of the Ovarian Cancer Microenvironment by SPARC

“…Conversely, MMP-2 and MMP-9 have been implicated in formation of ascites through induction of the release of VEGF by ovarian carcinoma cells (41), suggesting the existence of a positive autocrine feedback loop between VEGF and MMPs. A link between integrins and the up-regulated MMPs in SP À/À ascites may be suggested based on the earlier findings that a v h 3 integrin binds MMP-2 on the surface of melanoma and endothelial cells and both colocalize in caveolae and promote tumor growth and angiogenesis in vivo (60). a v h 3 integrin also cooperates with MMP-9 by increasing migration of metastatic breast cancer cells, as a v h 3 integrin does not adhere to native, intact collagen but it does adhere to collagen that has undergone proteolytic degradation due to exposure of an RGD binding site (61).…”

Tumor‐derived macrophage migration inhibitory factor modulates the biology of head and neck cancer cells via neutrophil activation

“…Many studies demonstrated that MMPs, in particular MMP9, are involved at several stages of cancer progression including neoangiogenesis and migration/metastasis of the tumor cells. 34,35 An association between tumor angiogenesis and neutrophils has been previously suggested. For instance, an influx of neutrophils was shown to foster tumor angiogenesis, whereas their depletion reduced angiogenesis in various animal tumor models.…”