Molecular diagnostics in melanoma

Carlson, J Andrew; Ross, Jeffery S.; Slominski, Andrzej; Linette, Gerald P.; Mysliborski, Judith; Hill, Jerome; Mihm, Martín C.

doi:10.1016/j.jaad.2004.08.034

Cited by 132 publications

(124 citation statements)

References 308 publications

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“…These effects had been observed in tumor cell lines of breast (39), prostate (40) and colon carcinoma (41). Melanoma is an aggressive form of skin cancer associated with high mortality and limited response to therapy once extended beyond the skin (42)(43)(44). Melatonin has been shown to suppress cell growth in selected cutaneous and uveal melanoma cell lines of rodent and human origin (32,(45)(46)(47).…”

Section: Introductionmentioning

confidence: 99%

Oncostatic effects of the indole melatonin and expression of its cytosolic and nuclear receptors in cultured human melanoma cell lines

Fischer

Żmijewski²,

Zbytek³

et al. 2006

Int J Oncol

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Abstract.Melatonin has been shown to have oncostatic effects on malignant melanoma in vitro and in vivo. We studied the growth suppressive effects of melatonin over a wide range of concentrations in four melanoma cell lines (SBCE2, WM-98, WM-164 and SKMEL-188) representative for different growth stages and phenotype. Melanoma cells were incubated with melatonin 10 -12 -10 -3 M, and proliferation and clonogenicity was assessed at 12 h and 14 days, respectively. We also determined the expression of cytosolic quinone oxidoreductases NQO1, NQO2 (known as MT3 receptor) and nuclear receptor ROR· by RT-PCR. Melatonin at pharmacological concentrations (10 -3 -10 -7 M) suppressed proliferation in all melanoma cell lines. In SKMEL-188 cells cultured in serum-free media, melatonin at low concentrations (10 -12 -10 -10 M) also slightly attenuated the proliferation. The effects of pharmacological doses of melatonin were confirmed in the clonogenic assay. Expression of NQO1 was detected in all cell lines, whereas NQO2 and nuclear receptor ROR· including its isoform ROR·4 were present only in SBCE2, WM-164 and WM-98. Thus, melatonin differentially suppressed proliferation in melanoma cell lines of different behaviour. The intensity of the oncostatic response to melatonin could be related to the cell-line specific pattern of melatonin cellular receptors and cytosolic binding protein expression.

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Section: Introductionmentioning

confidence: 99%

Oncostatic effects of the indole melatonin and expression of its cytosolic and nuclear receptors in cultured human melanoma cell lines

Fischer

Żmijewski²,

Zbytek³

et al. 2006

Int J Oncol

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“…In many cancers, both the overexpression of the growth factor and the receptor, besides mutations at the cytoplasmic tyrosine kinase domain, contribute to constitutive signaling; thus, these receptors make attractive targets for targeted therapies [80]. For example, in the transition from radial to vertical growth phase, melanoma as well as angiogenesis is heralded by both the expression and release of vascular endothelial growth factor (VEGF), which facilitates both growth of new blood and the tumor [29,81,82] …”

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confidence: 99%

“…Melanoma, like other cancers, arises because of accumulation of mutations in genes crucial for cell proliferation, cell differentiation, and cell death [28][29][30]. The factors influencing development and progression of melanoma include tumor initiation (mutations, loss of heterozygosity, gene amplification, gain and loss of chromosomes, gene silencing by methylation), growth (loss of cell cycle control, growth factors, neovascularization), resistance to apoptosis (inactivation of cell death pathways, gain of anti-apoptotic and survival factors), invasion and metastasis (cell motility, cell adhesion, proteolytic enzymes), and escape from immune surveillance (loss or gain of immune regulators) [29].…”

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confidence: 99%

Melanocyte Receptors: Clinical Implications and Therapeutic Relevance

Carlson

Linette

Aplin

et al. 2007

Dermatologic Clinics

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Melanocytes are an intraepidermal population of dendritic cells responsible for the production of melanin, a pigment that varies from yellow to brown to black pigment that after transfer to neighboring keratinocytes acts both as an endogenous screen and a buffering system against harmful ultraviolet (UV) wavelengths in sunlight [1]. Skin pigmentation has both individual and societal implications. The cosmetic desire for increased pigmentation (tanning) has resulted in many deleterious alterations including hastened skin ageing with wrinkles and poikiloderma and an increase in lentigines, melanocytic nevi, and melanoma. Focal or widespread loss of normal pigmentation not only renders individuals extraordinarily vulnerable to the harmful effects of sunlight (eg, increased risk of skin cancer in albinism), but it can also result in severe emotional stress and, in some societies, ostracism and discrimination (eg, vitiligo).Melanocytes are derived from the neural crest and are located along the basal layer of the epidermis and within the hair follicle, predominately the basal layer of the hair bulb matrix [1,2]. By the 50th day of intrauterine life, melanocytes can be detected in the epidermis; their migration to the epidermis and survival is dependent on receptor tyrosine kinase (RTK) c-Kit and its ligand stem cell factor (SCF) within the epidermis [3,4]. Mutations of the c-Kit gene lead to patches of hypopigmentation caused by lack of melanocyte migration, termed piebaldism [5]. Another important signaling molecule in melanocyte migration and development is Wnt5a, which signals via the Frizzled-5 receptor [6]. Overexpression of Wnt5a/ Frizzled is found in melanomas and associated with increased cell motility and invasiveness [7,8].Skin keratinocytes obtain melanin pigment from melanocytes, and keratinocytes provide the necessary microenvironment for melanocyte survival, proliferation, differentiation, and migration via production of ligands that interact with melanocyte receptors [1,[9][10][11] NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript epidermal melanin unit denotes the symbiotic relationship between one melanocyte transporting melanin via its dendritic processes to approximately 36 keratinocytes [10]. Melanocytes are located on the basement membrane among basal keratinocytes at ratio of 1 melanocyte per 5 basal keratinocytes in hematoxylin and eosin-stained histologic sections. This balance is maintained through regulated induction of melanocyte division. During childhood as the skin surface expands, throughout adulthood to maintain melanocyte numbers, and in response to exposure to sunlight or skin wounding, melanocytes are stimulated to proliferate at a low rate. Melanocyte proliferation entails uncoupling from keratinocytes, loss of their dendrites, cell division, migration along the basement membrane, then recoupling with keratinocytes to form the epidermal melanin unit. Keratinocytes regulate melanocyte growth and expression of melanocyte cell surface receptors via cell adhes...

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“…The rising incidence makes this cancer an issue of ever increasing clinical and economic importance and research interest (Garland et al, 2003;Tucker and Goldstein, 2003;Berwick et al, 2005). The identification of new prognostic markers may help to better distinguish low from high-risk disease apart from the classical histopathologic and clinical criteria (Carlson et al, 2005) and may offer new targets for therapy.…”

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confidence: 99%

FGFR4 Arg388 allele correlates with tumour thickness and FGFR4 protein expression with survival of melanoma patients

et al. 2006

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A single nucleotide polymorphism in the gene for FGFR4 (ÀArg388) has been associated with progression in various types of human cancer. Although fibroblast growth factors (FGFs) belong to the most important growth factors in melanoma, expression of FGF receptor subtype 4 has not been investigated yet. In this study, the protein expression of this receptor was analysed in 137 melanoma tissues of different progression stages by immunohistochemistry. FGFR4 protein was expressed in 45% of the specimens and correlated with pTNM tumour stages (UICC, P ¼ 0.023 and AJCC, P ¼ 0.046), presence of microulceration (P ¼ 0.009), tumour vascularity (P ¼ 0.001), metastases (P ¼ 0.025), number of primary tumours (P ¼ 0.022), overall survival (P ¼ 0.047) and disease-free survival (P ¼ 0.024). Furthermore, FGFR4 Arg388 polymorphism was analysed in 185 melanoma patients by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The Arg388 allele was detected in 45% of the melanoma patients and was significantly associated with tumour thickness (by Clark's level of invasion (P ¼ 0.004) and by Breslow in mm (P ¼ 0.02)) and the tumour subtype nodular melanoma (P ¼ 0.002). However, there was no correlation of the FGFR4 Arg388 allele with overall and disease-free survival. In conclusion, the Arg388 genotype and the protein expression of FGFR4 may be potential markers for progression of melanoma.

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Molecular diagnostics in melanoma

Cited by 132 publications

References 308 publications

Oncostatic effects of the indole melatonin and expression of its cytosolic and nuclear receptors in cultured human melanoma cell lines

Oncostatic effects of the indole melatonin and expression of its cytosolic and nuclear receptors in cultured human melanoma cell lines

Melanocyte Receptors: Clinical Implications and Therapeutic Relevance

FGFR4 Arg388 allele correlates with tumour thickness and FGFR4 protein expression with survival of melanoma patients

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