Modeling malignant melanoma in mice: pathogenesis and maintenance

Chin, Lynda

doi:10.1038/sj.onc.1203106

Cited by 15 publications

(8 citation statements)

References 56 publications

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“…Indeed its expression levels is elevated in human metastatic melanoma compared with primary melanoma 18,19 and in invasive HNSCC 20 . Recently, a role in mammary tumorigenesis has also been proposed for NEDD9, whose absence significantly impairs tumour formation induced by the polyoma virus middle T oncogene (PyMT) 21 (Table II).…”

Section: Integrin Adaptors In Cancermentioning

confidence: 99%

Integrin signalling adaptors: not only figurants in the cancer story

et al. 2010

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Current evidence highlights the ability of adaptor (or scaffold) proteins to create signalling platforms that drive cellular transformation upon integrin-dependent adhesion and growth factor receptor activation. The understanding of the biological effects regulated by these adaptors in tumours might be crucial for the identification of novel targets and the development of innovative therapeutic strategies for human cancer. In this review we will discuss the relevance of adaptor proteins in signalling originating from integrin-mediated cell-extracellular matrix (ECM) adhesion and growth factor stimulation within the context of cell transformation and tumour progression.Herein, we will specifically underline the contribution of p130CAS, NEDD9, CRK, and the IPP complex (ILK, PINCH and PARVIN) to cancer, along with the more recently identified p140CAP.

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Section: Integrin Adaptors In Cancermentioning

confidence: 99%

Integrin signalling adaptors: not only figurants in the cancer story

et al. 2010

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“…An elegant model for genetic investigations of spontaneous mouse melanoma has been derived in a hybrid mouse with activated Ras and with deletion of both Ink4a / arf products (4, 32). This model has recently been extended to demonstrate that Tyr‐Ras crossed onto a p53 null background also develop clinically similar spontaneous melanomas, supporting a role for p53 in melanomagenesis (7).…”

Section: Animal Models For Melanomamentioning

confidence: 99%

Animal Models of Melanoma: An HGF/SF Transgenic Mouse Model May Facilitate Experimental Access to UV Initiating Events

Noonan

Dudek

Merlino

et al. 2003

Pigment Cell Research

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Cutaneous malignant melanoma, the most lethal of the skin cancers, known for its intractability to current therapies, continues to increase in incidence, providing a significant public health challenge. There is a consensus that skin cancer is initiated by sunlight exposure. For non-melanoma skin cancer there is substantial evidence that chronic exposure to the ultraviolet B radiation (UVB) (280-320 nm) portion of the sunlight spectrum is responsible. Experimentally, UVB is mutagenic and chronic UVB exposure can cause non-melanoma skin cancer in laboratory animals. Non-melanoma tumors in animals and in humans show characteristic UVB signature lesions in the tumor suppressor p53 and ⁄ or in the patched (PTCH) gene. An action spectrum or wavelength dependence for squamous cell carcinoma in the mouse shows a major peak of efficacy in the UVB. For malignant melanoma, however, the situation is unclear and the critical direct target(s) of sunlight in initiating melanoma and even the wavelengths responsible are as yet unidentified. This lack of information is in major part a result of a paucity of animal models for melanoma which recapitulate the role of sunlight in initiating this disease. The epidemiology of melanoma differs significantly from non-melanoma skin cancer. Intense sporadic sunlight exposure in childhood, probably exacerbated by additional adult exposure, is associated with elevated melanoma risk. Melanoma is also a disease of gene-environment interactions with underlying genetic factors playing a significant role. These major differences indicate that extrapolation from information for nonmelanoma skin cancer to melanoma is unlikely to be useful. We summarize in this review the experimental information available on the role of UV radiation in melanoma and give an overview of animal melanoma models. A new model derived by neonatal UV irradiation of hepatocyte growth factor ⁄ scatter factor (HGF ⁄ SF) transgenic mice is described which recapitulates the etiology, the histopathology and molecular pathogenesis of human disease. It is anticipated that the HGF ⁄ SF transgenic model will provide a means to access the mechanism(s) by which sunlight initiates this lethal disease and provide an appropriate vehicle for derivation of appropriate therapeutic and preventive strategies.

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“…mutations in oncogenes, such as phosphatase and tensin homologue deleted on chromosome 10, Akt kinase, and Ras, inducing cellular proliferation have been identified. However, such mutations have rarely been detected in human melanomas and melanoma metastases (1,40). There is a considerable body of evidence from experimental mouse melanoma models that activating Ras mutations in combination with an inactivated INK4a/ARF (CDKN2a) tumor suppressor locus induce spontaneous melanomas with consecutive distant metastases in mice (40 -42).…”

Section: Figmentioning

confidence: 99%

Gene Expression Signatures for Tumor Progression, Tumor Subtype, and Tumor Thickness in Laser-Microdissected Melanoma Tissues

Jaeger

Koczan

Thiesen

et al. 2007

Clinical Cancer Research

212

193

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Purpose:To better understand the molecular mechanisms of malignant melanoma progression and metastasis, gene expression profiling was done of primary melanomas and melanoma metastases. Experimental Design: Tumor cell^specific gene expression in 19 primary melanomas and 22 melanoma metastases was analyzed using oligonucleotide microarrays after laser-capture microdissection of melanoma cells. Statistical analysis was done by random permutation analysis and support vector machines. Microarray data were further validated by immunohistochemistry and immunoblotting. Results: Overall, 308 genes were identified that showed significant differential expression between primary melanomas and melanoma metastases (false discovery rate V 0.05). Significantly overrepresented gene ontology categories in the list of 308 genes were cell cycle regulation, mitosis, cell communication, and cell adhesion. Overall, 47 genes showed up-regulation in metastases. These included Cdc6, Cdk1, septin 6, mitosin, kinesin family member 2C, osteopontin, and fibronectin. Down-regulated genes included E-cadherin, fibroblast growth factor binding protein, and desmocollin 1 and desmocollin 3, stratifin/14-3-3r, and the chemokine CCL27. Using support vector machine analysis of gene expression data, a performance of >85% correct classifications for primary melanomas and metastases was reached. Further analysis showed that subtypes of primary melanomas displayed characteristic gene expression patterns, as do thin tumors (V1.0 mm Breslow thickness) compared with intermediate and thick tumors (>2.0 mm Breslow thickness). Conclusions: Taken together, this large-scale gene expression study of malignant melanoma identified molecular signatures related to metastasis, melanoma subtypes, and tumor thickness. These findings not only provide deeper insights into the pathogenesis of melanoma progression but may also guide future research on innovative treatments.The incidence of malignant melanoma is steadily increasing with a present lifetime risk of 1 in 75 among the Caucasian population (1). The underlying factors for this phenomenon are largely unknown. After diagnosis of malignant melanoma, the single most important factor for the prognosis of melanoma patients is vertical tumor thickness as described earlier by Breslow (2). It could be shown that tumors of a few-millimeter thickness already show a high potential for metastasis with a fatal outcome for the patient. In the metastatic stage, melanoma patients have only few treatment options, consisting of monochemotherapies with dacarbazine (DTIC) or temozolomide, or polychemotherapy regimens combining DTIC with other chemotherapeutic agents such as cisplatin and 1,3-bis(2-chloroethyl)-1-nitrosourea (3 -5). Although significant clinical response rates were achieved by these treatment modalities, there was no substantial effect on the overall survival of these patients. Unfortunately, little is known about factors that contribute to the process of melanoma progression and metastasis.In recent years, DN...

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Modeling malignant melanoma in mice: pathogenesis and maintenance

Cited by 15 publications

References 56 publications

Integrin signalling adaptors: not only figurants in the cancer story

Integrin signalling adaptors: not only figurants in the cancer story

Animal Models of Melanoma: An HGF/SF Transgenic Mouse Model May Facilitate Experimental Access to UV Initiating Events

Gene Expression Signatures for Tumor Progression, Tumor Subtype, and Tumor Thickness in Laser-Microdissected Melanoma Tissues

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