Expression of matrilysin in vascular endothelial cells adjacent to matrilysin-producing tumors

Nagashima, Yoji; Hasegawa, S.; Koshikawa, Naohiko; Taki, Atsuko; Ichikawa, Yasushi; Kitamura, Hitoshi; Misugi, Kazuaki; Kihira, Yasunori; Matuo, Yuhsi; Yasumitsu, Hidetaro; Miyazaki, Kaoru

doi:10.1002/(sici)1097-0215(19970729)72:3<441::aid-ijc11>3.0.co;2-f

Cited by 56 publications

(29 citation statements)

References 27 publications

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“…Matrix metalloprotein 7 is commonly expressed by epithelialderived tumour cells, but immunohistochemical staining confirmed the RT -PCR data and showed that mesenchymal desmoid cells can also express this MMP. Also, vascular endothelial cells in desmoids expressed MMP7, which is similar as in MMP7-positive epithelial tumours (Nagashima et al, 1997).…”

Section: Discussionsupporting

confidence: 55%

Invasion and MMP expression profile in desmoid tumours

et al. 2004

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Desmoid tumours are locally invasive soft tissue tumours in which b-catenin mediated TCF-dependent transcription is activated. The role of soluble factors secreted by the myofibroblastic desmoid tumour, which could stimulate tumour invasiveness, was investigated. Using collagen gel invasion assays, the presence of factors stimulating invasion in desmoid conditioned media (CM) could be established. Since matrix metalloproteinases (MMPs) have been implicated in the process of tumoral invasion, the expression levels of the MMP family members were evaluated. Quantitative reverse transcription -PCR was used to determine the expression levels of MMP1, MMP2, MMP3, MMP7, MMP11, MMP12, MMP13, MMP14 and the inhibitors TIMP1, TIMP2 and TIMP3. Besides overexpression of MMP7, a known TCF-dependent target gene, a striking upregulation of the expression levels of MMP1, MMP3, MMP11, MMP12 and MMP13 in desmoid tumours, compared to unaffected fibroblasts from the same patients, was found. Treating the CM of desmoids with a synthetic and a physiologic MMP inhibitor reduced the invasion-stimulating capacity of the desmoid CM by approximately 50%. These results suggest the involvement of soluble factors, released by the desmoid cells, in stimulating invasion and implicate the MMPs as facilitators of invasion.

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Section: Discussionsupporting

confidence: 55%

Invasion and MMP expression profile in desmoid tumours

et al. 2004

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“…Angiogenesis is a process essential for tumor progression. MMP-7 mRNA and protein are found in vascular endothelial cells in close apposition to matrilysin-positive tumor cells (Nagashima et al, 1997). Furthermore, MMP-7 may accelerate the proliferation of human umbilical vein endothelial cells in a dose-dependent manner in vitro (Huo et al, 2002).…”

Section: Matrilysinsmentioning

confidence: 95%

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

Sbardella

Fasciglione

Gioia

et al. 2012

Molecular Aspects of Medicine

208

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a b s t r a c tHuman matrix metalloproteinases (MMPs) belong to the M10 family of the MA clan of endopeptidases. They are ubiquitarian enzymes, structurally characterized by an active site where a Zn 2+ atom, coordinated by three histidines, plays the catalytic role, assisted by a glutamic acid as a general base. Various MMPs display different domain composition, which is very important for macromolecular substrates recognition. Substrate specificity is very different among MMPs, being often associated to their cellular compartmentalization and/or cellular type where they are expressed. An extensive review of the different MMPs structural and functional features is integrated with their pathological role in several types of diseases, spanning from cancer to cardiovascular diseases and to neurodegeneration. It emerges a very complex and crucial role played by these enzymes in many physiological and pathological processes.

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“…In cancer tissues, various MMPs are overexpressed both in stromal and tumor cells. In contrast, matrilysin has been detected specifically in tumor cells but not in stromal cells (5,6). Among many MMPs, matrilysin appears to be one of the most important MMPs in human colon cancers because it is almost always overexpressed in colon cancers.…”

mentioning

confidence: 95%

Binding of Active Matrilysin to Cell Surface Cholesterol Sulfate Is Essential for Its Membrane-associated Proteolytic Action and Induction of Homotypic Cell Adhesion

Yamamoto

Higashi

Kioi

et al. 2006

Journal of Biological Chemistry

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Regulation of cell surface molecules by matrix metalloproteinases (MMPs), as well as MMPs-catalyzed degradation of extracellular matrix, is important for tumor invasion and metastasis. Our previous study (Kioi, M., Yamamoto, K., Higashi, S., Koshikawa, N., Fujita, K., and Miyazaki, K. (2003) Oncogene 22, 8662-8670) demonstrated that active matrilysin specifically binds to the surface of colon cancer cells and induces notable cell aggregation due to processing of the cell membrane protein(s). Furthermore, these aggregated cells showed a dramatically enhanced metastatic potential. To elucidate the mechanism of matrilysin-induced cell aggregation, we attempted to identify the matrilysin-binding substance on the cell surface. Here, we demonstrate that cholesterol sulfate on the cell surface is a major matrilysin-binding substance. We found that active matrilysin bound to the cell membrane and cholesterol sulfate incorporated into liposomes with similar affinities. Treatment of colon cancer cells with ␤-cyclodextrin significantly reduced not only matrilysin binding to the cell surface but also matrilysin-dependent proteolysis and cell aggregation. Interestingly, replenishment of cholesterol sulfate, but not cholesterol, neutralized the effects of ␤-cyclodextrin. Taken together, it is likely that binding of matrilysin to cholesterol sulfate facilitates the matrilysin-catalyzed modulation of cell surface proteins, thus inducing the cancer cell aggregation. Matrix metalloproteinases (MMPs)2 are zinc-dependent endopeptidases that degrade components of the extracellular matrix and play essential roles in tissue remodeling in physiological and pathological processes such as morphogenesis, differentiation, angiogenesis, tissue remodeling, and tumor invasion (1, 2). The association of MMPs with cancer cell invasion and metastasis has suggested that these proteinases represent attractive targets for the development of novel anti-tumor therapies.Recently, it has been suggested that the biological functions of various cell surface proteins are proteolytically modulated by several MMPs (1, 3, 4), including MT-MMPs, gelatinase A (MMP-2), gelatinase B (MMP-9), stromelysin (MMP-3), and matrilysin (MMP-7). These metalloproteinases are thought to regulate cellular functions by activating, inactivating, or releasing membrane proteins. Such regulation of cell surface molecules as well as MMP-catalyzed degradation of the extracellular matrix is important for tumor invasion and metastasis.Matrilysin is the smallest member of the MMP family, which lacks the C-terminal hemopexin-like domain. In cancer tissues, various MMPs are overexpressed both in stromal and tumor cells. In contrast, matrilysin has been detected specifically in tumor cells but not in stromal cells (5, 6). Among many MMPs, matrilysin appears to be one of the most important MMPs in human colon cancers because it is almost always overexpressed in colon cancers. Expression of matrilysin is also correlated well with malignancy and metastasis of cancers, especially in liver me...

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Expression of matrilysin in vascular endothelial cells adjacent to matrilysin-producing tumors

Cited by 56 publications

References 27 publications

Invasion and MMP expression profile in desmoid tumours

Invasion and MMP expression profile in desmoid tumours

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

Binding of Active Matrilysin to Cell Surface Cholesterol Sulfate Is Essential for Its Membrane-associated Proteolytic Action and Induction of Homotypic Cell Adhesion

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