Differences in expression of metalloproteinases and plasminogen activators in murine melanocytes and B16 melanoma variants: Lack of association with <i>In vitro</i> invasion

Huuzer, Jeannette C.; Uhlenkott, Carey E.; Meadows, Gary G.

doi:10.1002/ijc.2910630117

Cited by 10 publications

(5 citation statements)

References 32 publications

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“…45 Metalloproteinases play important roles in neoplastic processes, such as tumor invasion and metastases, 16 although conflicting results have been reported regarding the relation of MMP expression and the invasiveness of melanoma cells both in vitro and in an in vivo murine model. 46,47 Therefore, we analyzed the patterns of expression of MMP-2 and MMP-9 in benign lesions and in different stages of invasive growth of melanoma.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical expression of vascular endothelial growth factor, matrix metalloproteinase 2, and matrix metalloproteinase 9 in cutaneous melanocytic lesions

Simonetti

Lucarini

Brancorsini

et al. 2002

Cancer

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Postganglionic sympathetic neurons, which are exquisitely sensitive to small changes in levels of target‐derived nerve growth factor (NGF), express two transmembrane receptors: 1) the trkA receptor mediates neuron survival and neurite outgrowth; and 2) the p75 neurotrophin receptor (p75NTR) enhances neuronal responsiveness of trkA to NGF. Elevating levels of NGF induces several morphological and neurochemical alterations in sympathetic neurons, including axonal sprouting, increased levels of p75NTR mRNA relative to trkA mRNA, and increased accumulations of NGF in hypertrophied somata. Spontaneously hypertensive rats (SHR) display both elevated NGF levels and increased sympathetic axonal innervation of the mesenteric vasculature. In this investigation we assessed whether sympathetic neurons innervating the mesenteric vasculature of SHR display other features indicative of increased levels of target‐derived NGF. In 5‐week‐old SHR, levels of both p75NTR and trkA mRNA in mesenteric sympathetic neurons were significantly elevated compared to levels in age‐matched control rats. By 15 and 30 weeks of age, levels of p75NTR mRNA expression in mesenteric sympathetic neurons were similar between SHR and control rats. Accumulations of NGF were depleted in the sympathetic somata of 15‐ and 30‐week‐old SHR compared to age‐matched control rats. Moreover, sympathetic neurons in SHR were not hypertrophied, as the sizes of somata were comparable between SHR and control rats. Our data illustrate that despite having augmented levels of NGF in the mesenteric vasculature, SHR do not display many of the morphological and neurochemical features that are associated with an enhanced responsiveness by sympathetic neurons to elevated levels of target‐derived NGF. J. Comp. Neurol. 466:148–160, 2003. © 2003 Wiley‐Liss, Inc.

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Section: Discussionmentioning

confidence: 99%

Immunohistochemical expression of vascular endothelial growth factor, matrix metalloproteinase 2, and matrix metalloproteinase 9 in cutaneous melanocytic lesions

Simonetti

Lucarini

Brancorsini

et al. 2002

Cancer

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“…We examined the fibronectin levels of three different B16 melanoma cell lines, B16F1, B16F10, and B16BL6, which have increasing metastatic potential, respectively [34]. There was no correlation between the in vitro fibronectin expression of these cell lines and their malignant activity in vivo.…”

Section: Ag73 Effects On Breast Cancer and Melanoma Cell Metastasis Tmentioning

confidence: 99%

The laminin α-1 chain derived peptide, AG73, increases fibronectin levels in breast and melanoma cancer cells

Engbring

Hossain

VanOsdol

et al. 2008

Clin Exp Metastasis

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Laminin-111 promotes the malignant phenotype, and a 12-mer synthetic peptide (AG73, RKRLQVQLSIRT) from the carboxyl terminus of the alpha1 chain increases B16F10 melanoma metastasis to the lung and liver. Using an antibody array, fibronectin was identified as an up-regulated protein in B16F10 cells after incubation with this peptide. The increased fibronectin is cell-associated with no increase in soluble fibronectin. The AG73 peptide increased the number and size of bone metastases with both B16F10 melanoma and MDA-231 breast carcinoma cells in an intracardiac injection model. Using siRNA transfection, we found that a reduction in fibronectin expression did not reduce bone metastasis in the presence of the metastasis-promoting peptide AG73. We conclude that the laminin peptide AG73 increases metastasis independently of fibronectin expression.

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“…This may facilitate local invasion and release of tumour cells into the circulation. However, several experimental reports indicate that melanoma progression appears to be uPA rather than tPA-related (Quax et al, 1991;Meissauer et al, 1992;Huijzer et al, 1995;Shapiro et al, 1996). A possible stimulatory effect of tPA on angiogenesis might also enhance metastatic potential (Sato et al, 1993;Hu et al, 1994;Welling et al, 1996), although no influence of tPA on angiogenesis was found by others (Takei et al, 1995;Lansink et al, 1998;Sakamoto et al, 1998).…”

Section: mentioning

confidence: 99%

High tPA-expression in primary melanoma of the limb correlates with good prognosis

et al. 2000

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To investigate whether the course of primary melanoma disease correlates with expression of the various components of the proteolytic plasminogen activation (PA) system, immunohistochemical stainings for activators of plasminogen (tissue type (tPA) and urokinase type (uPA)), inhibitors of plasminogen activation (type 1 (PAI-1) and type 2 (PAI-2)) and the receptor for uPA (uPAR) were performed on 214 routinely processed melanoma lesions. All lesions were primary cutaneous melanomas, minimally 1.5 mm thick, and derived from patients with only local disease at the moment of diagnosis (clinically stage II (T 3–4 N 0 M 0), American Joint Committee on Cancer). Median patient follow-up was 6.1 years. Single variables as immunohistochemical staining results (extent of tumour cell staining, pattern of tumour cell staining and for some components also staining of stromal cells), histopathological and clinical parameters as well as treatment variables were analysed in order to assess their prognostic importance, in terms of time to recurrence, time to distant metastasis and duration of survival. The extent of tPA tumour cell positivity, categorized as 0–5%, 6–50% and 51–100%, appeared to be of importance for these end-points. Lesions with 51–100% tPA-positive tumour cells were found to have the best prognosis, whereas lesions with 6–50% tPA-positive tumour cells had the worst. Moreover, the prognostic significance of Breslow thickness, microscopic ulceration and sex was confirmed in this study. Multivariate analyses, incorporating these relevant factors, showed that the extent of tPA tumour cell positivity was an independent prognostic factor for distant metastasis-free interval (P= 0.012) and for the duration of survival (P= 0.043). © 2000 CancerResearch Campaign

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Differences in expression of metalloproteinases and plasminogen activators in murine melanocytes and B16 melanoma variants: Lack of association with In vitro invasion

Cited by 10 publications

References 32 publications

Immunohistochemical expression of vascular endothelial growth factor, matrix metalloproteinase 2, and matrix metalloproteinase 9 in cutaneous melanocytic lesions

Immunohistochemical expression of vascular endothelial growth factor, matrix metalloproteinase 2, and matrix metalloproteinase 9 in cutaneous melanocytic lesions

The laminin α-1 chain derived peptide, AG73, increases fibronectin levels in breast and melanoma cancer cells

High tPA-expression in primary melanoma of the limb correlates with good prognosis

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