Melanoma, tyrosinase

A, anti-oxidation activity evaluated by the neutralizing of DPPH as a model radical compound B, inhibition activity against mouse melanoma tyrosinase measured using L-DOPA as a substrate. Open circle, P-Arb closed circle, the coupling product (Arb-GA) open triangle, GA. 

Figure 12, Variation in lag time for tyrosine hy-droxylation hy hamster melanoma tyrosinase, (A) no DOPA (B) 4 X (C) 8 X (D) 1,6...

Marwan MM, Jiang JW, de Lauro Casttucci AM, Hadley ME (1990) Psoralen Stimulate Mouse Melanocyte and Melanoma Tyrosinase Activity in the Absence of Ultraviolet Light. Pigment Cell Res 3 214... 

Ponnazhagan and Kwon (1992) reported a putative tissue-specific ds-element (TE-1) located at-236 bp of the mouse tyrosinase promoter. They partially purified a TE-1 binding protein (approximately 49 kDa in size), but tissue specificity remains to be confirmed by a more detailed analysis. For the human tyrosinase promoter, Shibata et al. (1992) identified a 200-bp pigment cell-specific enhancer, located between -2.0 and -1.8 kb. A minimum core sequence of 39 bp was shown to be sufficient to confer the specific activity, although other regions (not identified so far) within the 200-bp fragment are required for more efficient expression in melanoma cells (Shibata et al., 1992). 

Bloom MB, Perry-Lalley D, Robbins PF, et al. Identification of tyrosinase-related protein 2 as a tumor rejection antigen for the B16 melanoma. J Exp Med 1997 185(3) 453 59. 

Tumor tissue has also been demonstrated to take up naked pDNA following direct intratumoral injection, but this ability may be dependent on tumor type and the pDNA construct. In an important study by Vile and Hart (1993), mice bearing subcutaneous (s.c.) B16F1 melanoma or Colo 26 colon carcinoma were injected intratumorally with naked P -gal pDNA or P -gal pDNA/calcium phosphate precipitates. The tumors were collected on days 2, 4, 6 and 10 after the pDNA intratumoral injection. A gradual increase in blue-staining cells was found in the transfected melanomas with 10-15% of the cells expressing /3-gal by day ten. In contrast, none of the colon carcinoma tumors was positive for /3-gal. One explanation for the lack of in vivo transfection of the colon carcinoma is that the /3-gal pDNA constmcts contained melanoma-specific promoters (tyrosinase and TRP promoters). This study demonstrated that using an appropriate promoter established tumors could take up and express naked pDNA. 

B. W. Hughes, A. H. Wells, Z. Bebok, V. K. Gadi, R. J. Garver, W. B. Parker, and E. J. Sorscher, Bystander killing of melanoma cells using the human tyrosinase promoter to express the Escherichia coli purine nucleoside phosphorylase gene, Cancer Res. 55 3339 (1995). 

Wittbjer, A., Odh, G., Rosengren, A. M., Rosengren, E., and Rorsman, H. (1989). Isolation of soluble tyrosinase from human melanoma cells. Acta Derm. Venereol. 69, 125-131. 

Catechol as an Activator of Tyrosinase. The phenolase activity of tyrosinase has been studied less completely than the catecholase activity, partly because of the lack of a satisfactory assay procedure. The phenolase reaction, however, is characterized by a lag time which can be abolished by adding dihydroxyphenylalanine (DOPA), the immediate product of the hydroxylation reaction 29S4, 102, 117), This phenomenon has been described by several investigators (29-34) and is illustrated in Figure 12, from Pomerantz and Warner (117), using the enzyme from Hamster melanoma. The same phenomenon has been analyzed by Duckworth and Coleman (102) for the mushroom enzyme. In the absence of DOPA, maximum velocity of the hydroxylase reaction is not reached for several minutes. Pomerantz and Warner (117) devised a convenient assay for the phenolase reaction by determining the radio-... 

Halaban R, Patton RS, Cheng E, Svedine S, Trombetta ES, Wahl ML, Ariyan S, Hebert DN. Abnormal acidification of melanoma cells induces tyrosinase retention in the early secretory pathway. J. Biol. Chem. 2002 277 14821-14828. 

Rusciano, D., Lorenzoni, P, Lin, S. and Burger, M. M. (1998b) HGF/SF and hepa-tocytes are potent downregulators of tyrosinase expression in B16 melanoma cells. J. Cell. Biochem. 77, 264-276. 

Some reports associate the rearrangement of dopachrome to DI in melanoma with an enzyme distal from tyrosinase (179-182) characterized as an oxidoreductase (183). Owing to the preliminary nature of the supporting experiments, however, the regulatory effect may be associated with the catalytic effect of metal ions rather than that of the new enzyme (184). 

P8. Pomerantz, 8. H., Separation, purification, and properties of two tyrosinases from hamster melanoma. J. Biol. Chem. 238, 2351-2357 (1963). 

The present review will focus on the analysis of l-DOPA and L-tyrosine by HPLC in plasma. Both are involved in the first step of melanogenesis controlled by a melanocyte-specific enzyme, tyrosinase. The plasma L-DOPA/L-tyrosine ratio has been evaluated as a tumor marker in melanoma during a 10-year collaboration between the Biochemistry Laboratory, the Dermatology Department of Saint-Louis Hospital (AP-HP) in Paris (France) and the Dermatology Department of the National Center of Oncology in Sofia (Bulgaria). 

Figure 4.1 Early phases of the melanogenesis pathway. The first steps are critically regulated by the melanocyte-specific enzyme tyrosinase. l-DOPA is directly formed from L-tyrosine (1) and/or indirectly via L-DOPAquinone (2). Adapted from Melanoma Research, 9, Letellier S, Gamier JP, Spy J, Stoitchkov K, Le Bricon T, Baccard M, Revol M, Kernels Y, Bousquet B. Development of metastases in mahgnant melanoma is associated with an increase of plasma L-DOPA/L-tyrosine ratio, pages 389-394, 1999, with permission from Lippincott Williams Wilkins...

T. Le Bricon, K. Stoitchkov, S. Letellier, F. Gtiibal, J. Spy, J.-P. Gamier, etal.. Simultaneous analysis of tyrosinase mRNA and markers of tyrosinase activity in the blood of patients with metastatic melanoma, Clin. Chim. Acta, 282, 101-113 (1999). 

Castanospermine s antitumor potential continues to receive attention. Recent in vitro studies have examined inhibition of tyrosinase activity in human melanoma cells (181), effects on intracellular transport of an avian erythroblastosis oncoprotein (277), and consequences for biosynthesis, maturation, and transport of ai-antitrypsin in the human hepatoma HepG2 cell line (257,272). The latter study was the first to show the inability of 239 to permeate the plasma membrane in intact HepG2 cells. In vivo experiments with nude mice proved that the alkaloid altered the glycosylation of endothelial cells, prevented angiogenesis, and inhibited tumor growth (273). However, recent in vivo studies failed to reveal cytotoxicity towards two rat prostate adenocarcinoma cell lines, or effects on cell characteristics related to metastatic potential (274). Uptake and metabolism of the more lipophilic 6-0-butanoylcastanospermine in tumor cell lines and after oral administration to mice was traced with C-labeled material, and showed rapid conversion into the parent alkaloid, which is undoubtedly the active metabolite (275). Multiple dosing in mice produced additive results. 

Tyrosinase may also play an important role in neuromelanin formation in the human brain, particularly in the substantia nigra, and could be central to dopamine neurotoxicity as well as contributing to the neurodegeneration associated with Parkinson s disease [6]. Melanoma-specific anticarcinogenic activity is known to be linked with tyrosinase activity [7]. 

Park YD et al. (2006) TXM13 human melanoma cells a novel source for the inhibition kinetics of human tyrosinase and for screening whitening agents. Biochem Cell Biol 84(1) 112-116... 

S-100 protein reactivity generally should be considered as melanomas. This is especially true if concomitant positivity is obtained for HMB-45, HMB-50, tyrosinase, or MART-1, because the latter four markers are only rarely associated with nerve sheath tumors. Despite the production of collagen type IV by nerve sheath cells, the immunohistochemical detection of this marker has limited value in the diagnosis of schwannian neoplasms because cells with smooth muscle, endothelial, and myo-fibroblastic differentiation may also synthesize it. 

Kaufmann O, Koch S, Burghardt J, et al. Tyrosinase, melan-A, and KBA62 as markers for the immunohistochemical identification of metastatic amelanotic melanomas in paraffin sections. Mod Pathol. 1998 11 740-746. 

Boyle JL, Haupt HM, Stern JB, et al. Tyrosinase expression in malignant melanoma, desmoplastic melanoma, and peripheral nerve sheath tumors. Arch Pathol Lab Med. 2002 126 816-822. 

FIGURE 7.14 Multifocal intense positivity for tyrosinase in metastatic epithelioid melanoma in the liver. 

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