Expression of matrilysin (matrix metalloproteinase-7) in primary cutaneous and metastatic melanoma

Kawasaki, Keishi; Kawakami, Tamihiro; Watabe, Hidenori; Itoh, Fumio; Mizoguchi, Masahiro; Soma, Yoshinao

doi:10.1111/j.1365-2133.2006.07678.x

Cited by 32 publications

(32 citation statements)

References 19 publications

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“…Among a number of options, we focused on ADAM9, MMP7 and osteopontin (OPN) for their important role in melanoma progression [16], [18], [19]. Growth and dissemination of human melanoma require a cascade of cellular processes including cellular interactions and proteolytic cleavage of growth factor ligands and extracellular matrix proteins.…”

Section: Resultsmentioning

confidence: 99%

“…In melanoma ADAM9 protein expression is restricted to the cells within the invading front, being detectable in tumor cells and in peritumoral stromal fibroblasts, and absent in fibroblasts distal to the tumor site [15]. Expression studies in primary cutaneous and metastatic melanomas also revealed MMP7 association with tumor cell invasion and progression suggesting its prognostic value in predicting the clinical behavior of melanoma [16].…”

Section: Introductionmentioning

confidence: 99%

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miR-126&126* Restored Expressions Play a Tumor Suppressor Role by Directly Regulating ADAM9 and MMP7 in Melanoma

et al. 2013

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The abnormal expression of several microRNAs has a causal role in tumorigenesis with either antineoplastic or oncogenic functions. Here we demonstrated that miR-126 and miR-126* play a tumor suppressor role in human melanoma through the direct or indirect repression of several key oncogenic molecules. The expression levels of miR-126&126* were elevated in normal melanocytes and primary melanoma cell lines, whereas they markedly declined in metastatic cells. Indeed, the restored expression of miR-126&126* in two advanced melanoma cell lines was accompanied by a significant reduction of proliferation, invasion and chemotaxis in vitro as well as of growth and dissemination in vivo. In accordance, the reverse functional effects were obtained by knocking down miR-126&126* by transfecting antisense LNA oligonucleotides in melanoma cells. Looking for the effectors of these antineoplastic functions, we identified ADAM9 and MMP7, two metalloproteases playing a pivotal role in melanoma progression, as direct targets of miR-126&126*. In addition, as ADAM9 and MMP7 share a role in the proteolytic cleavage of the HB-EGF precursor, we looked for the effectiveness of this regulatory pathway in melanoma, confirming the decrease of HB-EGF activation as a consequence of miR-126&126*-dependent downmodulation of ADAM9 and MMP7. Finally, gene profile analyses showed that miR-126&126* reexpression was sufficient to inactivate other key signaling pathways involved in the oncogenic transformation, as PI3K/AKT and MAPK, and to restore melanogenesis, as indicated by KIT/MITF/TYR induction. In view of this miR-126&126* wide-ranging action, we believe that the replacement of these microRNAs might be considered a promising therapeutic approach.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

miR-126&126* Restored Expressions Play a Tumor Suppressor Role by Directly Regulating ADAM9 and MMP7 in Melanoma

et al. 2013

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“…Notably, MMP-1 overexpression conferred an invasive and metastatic phenotype on early stage melanoma cells, whereas MMP-1 downregulation in late stage melanoma cells curtailed metastasis and angiogenesis (43, 44). Similarly, MMP-7 overexpression is often found in prostate and skin cancer (45–47) and may promote tumorigenesis by enhancing invasion, metastasis and cell proliferation (48–50). …”

Section: Discussionmentioning

confidence: 99%

14-3-3 Proteins Modulate the ETS Transcription Factor ETV1 in Prostate Cancer

Shin

Lightfoot

et al. 2013

Cancer Research

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Overexpression of the ETS-related transcription factor ETV1 can initiate neoplastic transformation of the prostate. ETV1 activity is highly regulated by phosphorylation, but the underlying mechanisms are unknown. Here we report that all 14-3-3 proteins, with the exception of the tumor suppressor 14-3-3σ, can bind to ETV1 in a condition manner dictated by its prominent phosphorylation site S216. All non-σ 14-3-3 proteins synergized with ETV1 to activate transcription of its target genes MMP-1 and MMP-7, which regulate extracellular matrix in the prostate tumor microenvironment. S216 mutation or 14-3-3τ downregulation was sufficient to reduce ETV1 protein levels in prostate cancer cells, indicating that non-σ 14-3-3 proteins protect ETV1 from degradation. Notably, S216 mutation also decreased ETV1-dependent migration and invasion in benign prostate cells. Downregulation of 14-3-3τ reduced prostate cancer cell invasion and growth in the same manner as ETV1 attenuation. Lastly, we showed that 14-3-3τ and 14-3-3ε were overexpressed in human prostate tumors. Taken together, our results demonstrated that non-σ 14-3-3 proteins are important modulators of ETV1 function that promote prostate tumorigenesis.

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“…Immunohistochemical detection of MMP-7, therefore, may serve as a tissue marker for benign melanocytic lesions [59]. Spitz nevi are benign, acquired moles derived from melanocytes (pigment cells) and cause concern because they were often confused with melanoma.…”

Section: Diagnostic Markersmentioning

confidence: 99%

Proteases in cutaneous malignant melanoma: relevance as biomarker and therapeutic target

Frőhlich

2010

Cell. Mol. Life Sci.

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Cutaneous malignant melanoma is the most aggressive skin cancer. It is also the most rapidly spreading cancer in terms of worldwide incidence. Although it is detected by simple inspection and can be relatively easily removed or treated, differential diagnosis to other melanocytic lesions, lack of prognostic markers, and no efficient treatment of advanced melanoma pose problems. Detection and targeting of proteases may represent a useful tool since they play a role in tumor cell metabolism, invasion, angiogenesis and metastasis. This review gives an overview of the role of proteases in development and progression of cutaneous malignant melanoma. In addition, regulation, activation, and interaction of proteases and their inhibitors are explained for tumors in general. The potential use of proteases as differential markers for melanoma mimicking melanocytic lesions, as biomarkers in tissues, and as prognostic serum markers is discussed. Current and future possibilities to target tumor proteases in therapy are presented.

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Expression of matrilysin (matrix metalloproteinase-7) in primary cutaneous and metastatic melanoma

Cited by 32 publications

References 19 publications

miR-126&126* Restored Expressions Play a Tumor Suppressor Role by Directly Regulating ADAM9 and MMP7 in Melanoma

miR-126&126* Restored Expressions Play a Tumor Suppressor Role by Directly Regulating ADAM9 and MMP7 in Melanoma

14-3-3 Proteins Modulate the ETS Transcription Factor ETV1 in Prostate Cancer

Proteases in cutaneous malignant melanoma: relevance as biomarker and therapeutic target

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