Expression of the c-Met/HGF receptor in human melanocytic neoplasms: demonstration of the relationship to malignant melanoma tumour progression

Natali, Pier Giorgio; Nicotra, Maria Rita; Renzo, Maria Flavia Di; Prat, María; Bigotti, A.; Cavaliere, R.; Comoglio, Paolo M.

doi:10.1038/bjc.1993.422

Cited by 181 publications

(134 citation statements)

References 23 publications

(26 reference statements)

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“…Although MET is normally activated in a paracrine manner, autocrine activation of HGF-MET has been described in melanoma progression (Li et al 2001;for review, see Vande Woude et al 1997). Accordingly, increased c-MET expression has been observed in metastatic melanoma (Natali et al 1993), and copy number gain of the c-MET locus at 7q33-qter seems to be a late event in melanoma progression (Wiltshire et al 1995;Bastian et al 1998). However, similar to EGFR above, neither focal MET amplifications nor activating MET point mutations have been detected in melanoma, although both have been observed in other human cancers Schmidt et al 1997;Kong-Beltran et al 2006;Smolen et al 2006).…”

Section: Receptor Tyrosine Kinase (Rtks) Activationmentioning

confidence: 86%

Malignant melanoma: genetics and therapeutics in the genomic era

2006

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Cell for cell, probably no human cancer is as aggressive as melanoma. It is among a handful of cancers whose dimensions are reported in millimeters. Tumor thickness approaching 4 mm presents a high risk of metastasis, and a diagnosis of metastatic melanoma carries with it an abysmal median survival of 6-9 mo. What features of this malignancy account for such aggressive behavior? Is it the migratory history of its cell of origin or the programmed adaptation of its differentiated progeny to environmental stress, particularly ultraviolet radiation? While the answers to these questions are far from complete, major strides have been made in our understanding of the cellular, molecular, and genetic underpinnings of melanoma. More importantly, these discoveries carry profound implications for the development of therapies focused directly at the molecular engines driving melanoma, suggesting that we may have reached the brink of an unprecedented opportunity to translate basic science into clinical advances. In this review, we attempt to summarize our current understanding of the genetics and biology of this disease, drawing from expanding genomic information and lessons from development and genetically engineered mouse models. In addition, we look forward toward how these new insights will impact on therapeutic options for metastatic melanoma in the near future. The diseaseMelanomas most often arise within epidermal melanocytes of the skin, although they can also derive from noncutaneous melanocytes such as those lining the choroidal layer of the eye, GI and GU mucosal surfaces, or the meninges. Melanoma is also among the more common causes of "metastatic cancer of unknown primary," which may reflect either a propensity to arise in unexpected sites along the neural crest migratory route, or rapid growth of poorly differentiated lesions arising from indolent or unrecognized cutaneous primary lesions. Clinical staging for primary cutaneous melanoma employs measurements of thickness (in millimeters), presence of ulceration, penetration through cutaneous layers, mitotic rate, evidence of "in transit" metastasis, tumor spread to draining lymph nodes, and evidence of distant metastasis. Management issues in melanoma can be classified in terms of prevention, diagnosis, local disease management, and treatment of metastatic disease.In view of the epidemiological and emerging experimental evidence linking melanoma incidence to UV exposure and skin phototype, prevention and screening strategies represent key areas for reduction of disease incidence and severity. For most cutaneous melanomas in the so-called radial growth phase (e.g., thin melanomas), surgical removal affords curative treatment. In contrast, a significant fraction of patients diagnosed with intermediate-thickness (2-4 mm) cutaneous melanoma eventually succumb to recurrence at regional or distant sites.Critical biological questions facing the melanoma research community include: (1) What genetic and environmental factors contribute to and/or modulate risk of melanom...

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Section: Receptor Tyrosine Kinase (Rtks) Activationmentioning

confidence: 86%

Malignant melanoma: genetics and therapeutics in the genomic era

2006

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“…Because of its varied biological properties, the expression of HGF/SF in tumours may well act to enhance cell growth and spread and to stimulate metastasis. An increasing number of reports have recorded that both HGF/SF and its receptor, Met, are expressed, and often overexpressed, in various cancers, such as bladder, lung, pancreas, thyroid, colon and stomach carcinoma (Di Renzo et al, 1991Prat et al, 1991;Natali et al, 1993;Joseph et al, 1995). In breast cancer, the level of HGF/SF associated with tumour material has been reported to be a strong indicator of recurrence and predictor of survival (Yamashita et al, 1994 (Rong et al, 1992).…”

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confidence: 99%

Expression of HGF/SF in mesothelioma cell lines and its effects on cell motility, proliferation and morphology

Harvey

Warn²,

Dobbin³

et al. 1998

Br J Cancer

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Summary The expression of hepatocyte growth factor/scatter factor (HGF/SF) was studied in 12 BR became more elongated and bipolar, while BT formed more spread-out cell colonies. HGF/SF acted as a paracrine effector on the epithelioid BT cells and stimulated both cell-spreading and proliferation. Interestingly, BT cells spread but did not scatter in response to exogenous HGF/SF. In contrast BR cells showed only some stimulation of cell motility with HGF/SF and no increase in cell proliferation was observed. Because HGF/SF was previously found in the pleural effusion fluids of patients with malignant mesothelioma and in paraffinembedded tumour tissues, it is concluded that HGF/SF may well stimulate the growth and spread of malignant mesothelioma in vivo by paracrine and/or autocrine mechanisms.

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“…HGF has been shown to stimulate growth and invasiveness in tumor cells and aberrant HGF/c-Met signaling is implicated in a large number of human cancers including melanomas (Trusolino and Comoglio, 2002). HGF is a mitogen of human melanocytes and overexpression of c-Met correlates with the invasive growth phase of melanoma cells (Natali et al, 1993). Recent studies by Herlyn's group has shown that most of melanoma cells, but not normal melanocytes, produce HGF, which can induce sustained activation of its receptor (Li et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

HGF induces fibronectin matrix synthesis in melanoma cells through MAP kinase-dependent signaling pathway and induction of Egr-1

et al. 2004

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The matrix fibronectin protein is a multifunctional adhesive molecule that promotes migration and invasiveness of many tumors including melanomas. Increased fibronectin synthesis has been associated with the metastatic potential of melanoma cells; however, the molecular mechanisms underlying fibronectin overexpression during melanoma development are poorly understood. We report that hepatocyte growth factor/scatter factor (HGF) induces fibronectin expression and its extracellular assembly on the surface of melanoma cells through activation of mitogen-activated protein (MAP) kinase pathway, and induction and transcriptional activation of Early growth response-1 (Egr-1). Inhibition of B-RAF/ MAP kinase pathway by dominant-negative mutants and by U0126-abrogated HGF-induced Egr-1, and chromatin immunoprecipitation showed that Egr-1 is bound to the fibronectin promoter in response to HGF. Exogenously expressed Egr-1 increased fibronectin levels, while blockage of Egr-1 activation by expression of the Egr-1 corepressor NAB2 interfered with the upregulation of fibronectin synthesis induced by HGF, indicating that Egr-1 exerts a significant role in fibronectin expression in response to HGF. Finally, analysis of the expression pattern of fibronectin in melanoma cells demonstrated that fibronectin levels are correlated with constitutive MAP kinase signaling. Our data define a novel mechanism that might have important implications in regulation of melanoma progression by autocrine HGF signaling or by constitutive activation of MAP kinase pathway.

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Expression of the c-Met/HGF receptor in human melanocytic neoplasms: demonstration of the relationship to malignant melanoma tumour progression

Cited by 181 publications

References 23 publications

Malignant melanoma: genetics and therapeutics in the genomic era

Malignant melanoma: genetics and therapeutics in the genomic era

Expression of HGF/SF in mesothelioma cell lines and its effects on cell motility, proliferation and morphology

HGF induces fibronectin matrix synthesis in melanoma cells through MAP kinase-dependent signaling pathway and induction of Egr-1

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