Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An improved bubble method was developed for applying an ultrathin layer of nuclear track emulsion on the surface of cells labeled with I125-MSH. The autoradiographs of I125-MSH binding indicate a nonrandom distribution of receptors on the surface of mouse melanoma cells. It is suggested that MSH receptors are displayed in clusters previous to and independently of their exposure to the hormone.
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PMID:Nonrandom distribution of receptors for melanocyte-stimulating hormone on the surface of mouse melanoma cells. 17 35

Growth and melanization are intimately related in melanoma cells. MSH, by promoting elevated cyclic AMP levels, causes increases in melanization, cessation of growth, and gross morphologic changes in Cloudman S-91 melanoma cells. Growth inhibition results from high levels of cyclic AMP while growth stimulation occurs with lower levels. During melanization, oxidation products of tyrosine are generated which are toxic to the cells. Genetic studies have revealed that some of these processes are related through common biochemical pathways. This article reviews work of recent years on such regulatory mechanisms in melanoma.
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PMID:Factors regulating growth and pigmentation of melanoma cells. 17 4

The proliferation of human melanocytes in vitro was stimulated by MSH. This stimulation was further intensified by the simultaneous addition of theophylline with MSH. Theophylline alone stimulated proliferation moderately. Dibutyryl cyclic AMP strongly stimulated the proliferation, but sodium butyrate, 5'-AMP and cGMP did not. The stimulation by dibutyryl cyclic AMP was continued up to 4 days so far tested. These findings are directly opposed to those on mouse melanoma cells in culture which responded with retarded growth to MSH and cyclic AMP. It is suggested that the difference of proliferation control may explain the different reaction of the melanocyte and the melanoma cells. The epidermal melanocytes seem to belong to the exceptional group of the cells which responded to cyclic AMP with accelerated proliferation.
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PMID:Stimulation by melanocyte stimulating hormone and dibutyryl adenosine 3'5'-cyclic monophosphate of DNA synthesis in human melanocytes in vitro. 18 88

A hybrid toxin targeted to melanotropin receptors and selectively cytotoxic to melanoma cell lines in vitro has recently been developed. The toxin, a recombinant fusion protein (designated DAB389-MSH), contains the peptide sequences of alpha-melanocyte-stimulating hormone (alpha-MSH) and the catalytic (cytotoxic; Fragment A) and lipophilic (part of Fragment B) domains of diphtheria toxin. In the present study, binding of DAB389-MSH to melanotropin receptors in biopsy specimens of human and mouse melanoma metastases was assessed by measuring its ability to inhibit binding of a radiolabeled, superpotent analogue of alpha-MSH (125I-[Nle4,D-Phe7]-alpha-MSH; 125I-NDP-MSH) and comparing its potency in this system with those of the established ligands NDP-MSH and alpha-MSH. Radioligand binding to tissue sections in vitro was localized and quantified by autoradiography and image analysis. DAB389-MSH inhibited binding of 125I-NDP-MSH to experimental murine B16-F1C23 melanoma metastasis tissue and to melanoma metastases of three patients. In both mouse and human melanoma tissues, concentration-response relationships for DAB389-MSH-mediated inhibition of 125I-NDP-MSH binding were parallel, and its maximal effects were comparable in magnitude, to those of NDP-MSH and alpha-MSH. Half-maximal peptide concentrations for inhibition of 125I-NDP-MSH binding to mouse melanoma tissue sections were: NDP-MSH, 0.63 nM; alpha-MSH, 3.14 nM; and DAB389-MSH, 10.1 nM. In human melanoma tissues, the respective half-maximal peptide concentrations for inhibition of 125I-NDP-MSH binding to mouse melanoma tissue sections were: NDP-MSH, 1.80 nM; alpha-MSH, 2.43 nM; and DAB389-MSH, 11.9 nM. Taken together, these results suggest that NDP-MSH, alpha-MSH, and DAB389-MSH bind to a common melanotropin receptor in human metastatic melanoma cells. Since previous work has shown that melanotropin receptors are detectable in melanoma metastases of about 80% of human patients, malignant melanoma cells of many patients may be susceptible to killing by the melanotropin receptor-targeted cytotoxin DAB389-MSH.
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PMID:Interaction of an alpha-melanocyte-stimulating hormone-diphtheria toxin fusion protein with melanotropin receptors in human melanoma metastases. 131 97

Our previous work indicated that IR-alpha-MSH (immunoreactive alpha-melanocyte-stimulating hormone) plasma levels are three times as high in melanoma patients with progressing disease than in disease-free patients, and that the melanoma tumor itself may be the source of IR-alpha-MSH. Further identification of the material in tumor extracts has been carried out in this study, and the results presented here show that the immunoreactivity is associated with a major fraction of about 16 kDa and another of 5-9 kDa. Significant amounts of the immunoreactive material were also found in human melanoma cells but not in culture supernatants. The presence of this material may be related to the melanogenic status of the tumor cells. We have estimated the intracellular IR-alpha-MSH to be within a 0.4 to 2.3 nM range in melanoma tumor cells. We have investigated the melanogenic effect of the IR-alpha-MSH material and its relationship to alpha-MSH. Purified extracts both from metastases and cultured cells were found to promote frog skin darkening as well as tyrosinase activity in Cloudman S91 melanoma cells. The IR material could also displace labeled alpha-MSH from its binding sites in human melanoma cells. Our data clearly indicate that melanoma cells engage in an autocrine production of alpha-MSH-like bioactive peptides by melanoma cells, of larger mol.wt., which are able to bind to MSH receptors. These peptides may be involved in the regulation of melanogenesis and possibly in the growth and proliferation of melanoma cells by an autocrine/paracrine mechanism.
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PMID:Partial characterization of IR-alpha-MSH peptides found in melanoma tumors. 133 93

Melanocyte stimulating hormone (alpha-MSH, alpha-melanotropin),Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Ly-Pro-Va l-NH2, regulates melanogenesis within epidermal melanocytes of many animals. An MSH analogue ([Nle4,D-Phe7]alpha-MSH) that exhibits superpotency and prolonged biological activity has been synthesized, biologically characterized, and is presently in clinical trials to determine its possible clinical use in tanning of the skin. It also has potential for the diagnosis, localization, and chemotherapy of melanoma. The effects of this analogue on the growth, metastatic behavior, and invasive potential of a melanotic variant of Cloudman S-91 murine melanoma are reported here. In an intracutaneous murine model of melanoma cell tumor growth, the analogue did not increase primary tumor growth (size) after the period of administration of the peptide hormone analogue and did not affect spontaneous lung metastases. Survival times for the control and melanotropin-treated groups were similar, suggesting that overall tumor burden was not affected by treatment with the hormone analogue. Last, melanoma cell invasion through a human amniotic basement membrane in vitro was not enhanced compared to untreated cells.
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PMID:Effects of a melanotropic peptide on melanoma cell growth, metastasis, and invasion. 133 2

Tyrosinase induction in murine malignant melanocytes by alpha MSH is well known, but its molecular basis has not been characterized. Treatment of B16 melanoma cells with theophylline or alpha MSH mediates a larger induction of tyrosine hydroxylase than of dopa oxidase activity in total cell extracts, and in the melanosomal and microsomal fractions. No evidence for the modulation of a tyrosinase effector was found. SDS-PAGE and specific activity stain demonstrated two forms of tyrosinase, with different degrees of induction by theophylline. These results agree with the recent proposal that two tyrosinases, encoded by different genes, are present in murine melanocytes.
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PMID:Melanocyte stimulating hormone activation of tyrosinase in B16 mouse melanoma cells. Evidence for a differential induction of two distinct isoenzymes. 135 58

MSH can up-regulate MSH binding capacity of cultured Cloudman melanoma cells in a dose- and time-dependent fashion. Binding is mediated through proteins exhibiting an apparent molecular weight of 50-53kDa, consistent with previous studies implicating them as the principal MSH receptors on Cloudman cells. Pre-incubation of cells with MSH stimulates expression of the receptor proteins both on the plasma membrane surface as well as in internal sites associated with coated vesicles. The effects of MSH are additive with those of UV light, suggesting that UV and MSH might stimulate receptor expression through separate mechanisms.
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PMID:Up-regulation of MSH receptors by MSH in Cloudman melanoma cells. 144 64

A novel chelating derivative of alpha melanocyte stimulating hormone, bis MSH-DTPA, has been used for the diagnostic targeting of malignant melanoma. 15 patients were investigated of whom nine were shown by other means to have active disease at the time of the scan. Tumours were imaged in all of these nine patients. Of a total of 46 lesions over 10 mm encountered, 41 (89%) were imaged. There were no false positives and in two cases bisMSH-DTPA was instrumental in reversing diagnoses made using ultrasound. Derivatives of melanocyte stimulating hormone may be of considerable value in targeting melanomas.
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PMID:The use of a chelating derivative of alpha melanocyte stimulating hormone for the clinical imaging of malignant melanoma. 154 Aug

MSH receptors on mouse melanoma tissue sections were quantified by receptor autoradiography, yielding results which were very similar to those obtained by a conventional receptor binding assay with isolated cells. In order to minimize non-specific binding, it proved to be crucial to use a radioactive monoiodinated MSH radioligand retaining full biological activity and to apply the binding conditions developed for isolated cells to the incubation of whole tissue sections. The displacement curves obtained after quantitative analysis of autoradiograms from tissue sections yielded a KD-value of the same order of magnitude (0.58 nM; average of n = 7 experiments) as those obtained in the normal binding assay with isolated cells (1.2 nM; average of n = 10 experiments). Similarly, receptor numbers per cell on tissue sections (14,700; n = 7) did not differ markedly from those determined with isolated cells (10,500; n = 10). These results demonstrate that receptor autoradiography can be applied to the quantification of peptide hormone receptors on peripheral tissues.
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PMID:Quantification of MSH receptors on mouse melanoma tissue by receptor autoradiography. 165 38


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