Matrix metalloproteinase‐2 (MMP‐2) immunoreactive protein—a new prognostic marker in uveal melanoma?

Väisänen, Anne; Kallioinen, Matti; Dickhoff, Kai von; Laatikainen, Leila; Höyhtyä, Matti; Turpeenniemi‐Hujanen, Taina

doi:10.1002/(sici)1096-9896(199905)188:1<56::aid-path304>3.3.co;2-2

Cited by 20 publications

(36 citation statements)

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“…MMPs are implicated in this process by their expression in and around forming blood vessels (Blood and Zetter, 1990) and by their ability to modulate endothelial cell proliferation and microtubule formation in vitro (Karelina et al, 1995). Moreover, MMP-2 activity has been shown to correlate with metastatic potential in melanoma (Frisch and Morisaki, 1990;Hofmann et al, 1999;Vaisanen et al, 1998Vaisanen et al, , 1999, and its promoter contains at least one AP- Figure 8 Tumor microvessel density (MVD) of SB2-AP-2B or neo-transfected SB2 melanomas in vivo. Cells were injected s.c. into groups of nude mice (n=5).…”

Section: Discussionmentioning

confidence: 99%

“…(Liotta, 1980(Liotta, , 1986. Expression of the 72 Da type IV collagenase, also known as MMP-2 or gelatinase A, has been shown to correlate with metastatic potential in melanoma (Frisch and Morisaki, 1990;Hofmann et al, 1999;Vaisanen et al, 1998Vaisanen et al, , 1999 Interestingly, the MMP-2 promoter has been cloned and sequenced, and contains at least one AP-2 binding element (Frisch and Morisaki, 1990;Qin et al, 1999;Somasundaram et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

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Dominant-negative transcription factor AP-2 augments SB-2 melanoma tumor growth in vivo

et al. 2001

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We have previously demonstrated that the transition of melanoma to the metastatic phenotype is associated with a loss of expression of the transcription factor AP-2. To further investigate the role of AP-2 in the progression of human melanoma, we attempted to inactivate AP-2 in primary cutaneous SB-2 melanoma cells by using a dominant-negative AP-2, or AP-2B, gene. AP-2B is an alternatively spliced AP-2 variant capable of inhibiting AP-2 trans-activator function. Stable transfection of primary cutaneous melanoma SB-2 cells with the dominant-negative AP-2B gene was con®rmed by RT ± PCR and Northern blot analyses. Electromobility shift assay using nuclear extracts from these cell lines demonstrated decreased functional binding of AP-2B-transfected cells to the AP-2 consensus binding sequence compared with neo-transfected controls. In addition, CAT activity driven by a construct containing the AP-2 consensus binding sequence was downregulated in the AP-2B transfected cells, indicating AP-2 activity was quenched in the transfected cells. Orthotopic (subcutaneous) injection of the dominant-negative (AP-2B)-transfected cell lines into nude mice increased their tumorigenicity compared to control neo-transfected cells. The AP-2B-transfected cells displayed an increase in MMP-2 expression (by Northern blot) and MMP-2 activity (by zymography), which resulted in an increase in invasiveness through Matrigel-coated ®lters. The AP-2B-transfected tumors also displayed an increase in MMP-2 expression, microvessel density, and angiogenesis in vivo. These results demonstrate that inactivation of AP-2 contributes to the progression of melanoma, at least partially via deregulation of the MMP-2 gene.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dominant-negative transcription factor AP-2 augments SB-2 melanoma tumor growth in vivo

et al. 2001

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“…Expression of MMP-1 is associated with lymphvascular invasion and lymph node metastasis in stage IB cervical cancer 59 and peritoneal metastasis in gastric cancer. 60 Expression of MMP-2 in tumour cells can indicate increased risk of metastasis in uveal melanoma 61 and in SCC of tongue. 62 The expression of MMP-7 in tumour cells is associated with liver and lymph node metastasis in gastric carcinomas.…”

Section: Mmps As Predictors Of Recurrence or Metastasis Riskmentioning

confidence: 99%

“…94 Increased expression levels of MMP-2 in tumour cells is related to poor survival in gastric cancer, 95 hypopharyngeal SCC, 96 ovarian cystadenocarcinoma, 97 adenocarcinoma 31 and nonsmall cell carcinoma of the lung, 98 ovarian 54 and cervical carcinoma, 37 bladder carcinoma, 49 urothelial 99 and renal carcinoma, 100 breast carcinoma 101 and uveal melanoma. 61 However, Ring et al 102 found no correlation between positivity of tumour cells for MMP-2 or MMP-9 and tumour stage or overall survival in 212 patients with colorectal carcinoma.…”

Section: Mmps As Prognostic Survival Markers In Cancermentioning

confidence: 99%

Matrix metalloproteinases in cancer: Prognostic markers and therapeutic targets

Vihinen

Kähäri

2002

Intl Journal of Cancer

582

484

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Degradation of extracellular matrix is crucial for malignant tumour growth, invasion, metastasis and angiogenesis. Matrix metalloproteinases (MMPs) are a family of zinc-dependent neutral endopeptidases collectively capable of degrading essentially all matrix components. Elevated levels of distinct MMPs can be detected in tumour tissue or serum of patients with advanced cancer and their role as prognostic indicators in cancer is studied. In addition, therapeutic intervention of tumour growth and invasion based on inhibition of MMP activity is under intensive investigation and several MMP inhibitors are in clinical trials in cancer. In this review, we discuss the current view on the feasibility of MMPs as prognostic markers and as targets for therapeutic intervention in cancer.

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“…By interfering with the ability of actin microfilaments to transduce forces throughout the tumor cell, it was possible to block the constriction of matrices reversibly with 1 mol/L cytochalasin-D. Uveal melanoma cell lines have been shown to secrete gelatinolytic metalloproteinases, 143,144 and there is evidence associating expression of metalloproteinase-2 to metastases from uveal melanoma. 145 There are no known physiological analogs of vasculogenic mimicry. In fact, the generation of vascular channels by cytotrophoblasts in placental tissue 146 -148 may represent the last normal vasculogenic event in the human.…”

Section: Therapeutic Approaches Targeting Vasculogenic Mimicrymentioning

confidence: 99%

Vasculogenic Mimicry and Tumor Angiogenesis

Folberg

Hendrix

Maniotis

2000

The American Journal of Pathology

632

434

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Tumors require a blood supply for growth and hematogenous dissemination. Much attention has been focused on the role of angiogenesis-the recruitment of new vessels into a tumor from pre-existing vessels. However, angiogenesis may not be the only mechanism by which tumors acquire a microcirculation. Highly aggressive and metastatic melanoma cells are capable of forming highly patterned vascular channels in vitro that are composed of a basement membrane that stains positive with the periodic acid-Schiff (PAS) reagent in the absence of endothelial cells and fibroblasts. These channels formed in vitro are identical morphologically to PAS-positive channels in histological preparations from highly aggressive primary uveal melanomas, in the vertical growth phase of cutaneous melanomas, and in metastatic uveal and cutaneous melanoma. The generation of microvascular channels by genetically deregulated, aggressive tumor cells was termed "vasculogenic mimicry" to emphasize their de novo generation without participation by endothelial cells and independent of angiogenesis. Techniques designed to identify the tumor microcirculation by the staining of endothelial cells may not be applicable to tumors that express vasculogenic mimicry. Although it is not known if therapeutic strategies targeting endothelial cells will be effective in tumors whose blood supply is formed by tumor cells in the absence of angiogenesis, the biomechanical and molecular events that regulate vasculogenic mimicry provide opportunities for the development of novel forms of tumor-targeted treatments. The unique patterning characteristic of vasculogenic mimicry provides an opportunity to design noninvasive imaging techniques to detect highly aggressive neoplasms and their metastases. Tumors require a blood supply to sustain growth. The tumor microcirculation plays a central role in the hematogenous dissemination of cancers. Considerable attention has been focused on the mechanisms by which tumors acquire their blood supply. It is a well-accepted paradigm that tumors recruit new blood vessels from the existing circulation 1 -angiogenesis-either from factors secreted by the tumor cells, as Folkman 2,3 has emphasized, or from surrounding stromal cells. 4 There are two variations on the theme of tumor angiogenesis: augmentation of the angiogenic response by progenitor endothelial cells, and vessel cooption. Asahara and associates 5 described the incorporation of endothelial cell progenitors (or angioblasts) from circulating peripheral blood into sites of ischemic-driven angiogenesis. Holash and associates 6 described a process of "vessel cooption" in which tumors coopt the existing vasculature, which regresses leading to massive necrosis, and the tumor is then vascularized at the periphery by tumor angiogenesis as described above.We 7 recently described a novel process by which tumors develop a highly patterned microcirculation that is independent of angiogenesis: in aggressive primary and metastatic melanomas, the tumor cells generate acellular microcirculat...

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Matrix metalloproteinase‐2 (MMP‐2) immunoreactive protein—a new prognostic marker in uveal melanoma?

Cited by 20 publications

References 0 publications

Dominant-negative transcription factor AP-2 augments SB-2 melanoma tumor growth in vivo

Dominant-negative transcription factor AP-2 augments SB-2 melanoma tumor growth in vivo

Matrix metalloproteinases in cancer: Prognostic markers and therapeutic targets

Vasculogenic Mimicry and Tumor Angiogenesis

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