The natural history of a family of transplantable melanomas in hamsters

Bomirski, A; Słomiński, Andrzej; Bigda, Jacek

doi:10.1007/bf00046481

Cited by 68 publications

(86 citation statements)

References 118 publications

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“…Since investigated cells had the same genotype our results clearly demonstrate that melanin and/or active melanogenesis is responsible for melanoma radioresistance. These in vitro studies provide support for future experiments using animal models of melanotic and amelanotic transplantable melanomas linked by common origin 46 and human melanotic melanomas transplanted into immunodeficient mice.…”

Section: Discussionmentioning

confidence: 62%

Inhibition of melanogenesis as a radiation sensitizer for melanoma therapy

Brożyna¹,

VanMiddlesworth²,

Slominski³

2008

Intl Journal of Cancer

119

113

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Melanin pigment displays strong photo-and radioprotective properties, suggesting that inhibition melanogenesis could increase sensitivity of melanoma to ionizing radiation. We tested this concept in human melanoma cells cultured in either Ham's F10 medium to maintain amelanotic phenotype or DMEM to induce/stimulate melanin production, respectively; N-phenylthiourea (PTU) and Dpenicillamine were used as an inhibitor of melanogenesis. Melanogenic activity was evaluated by visual inspection (color of cell pellets) or by measurement of tyrosinase (dopa oxidase) activity assay. Amelanotic cells or cells with various melanin content were exposed to gamma radiation and tested for viability and colony forming capability. Gamma radiation at doses of 2-15 Gy inhibited cell viability and colony forming efficiency in dose-and timedependent manner, but pigmented melanoma cells were significantly more resistant to gamma radiation than nonpigmented cells (p < 0.05-0.001). Both PTU and D-penicillamine inhibited strongly tyrosinase activity and melanin production in melanoma cells (p < 0.05-0.001). Furthermore, inhibition of melanogenesis by PTU or D-penicillamine resulted in enhancement of melanoma cells sensitivity to killing by gamma rays. In conclusion, the results of these cell culture experiments give support to a clinical trial of pharmacologically induced decrease in melanin synthesis to enhance the efficacy of radiotherapy in advanced melanomas. ' 2008 Wiley-Liss, Inc.Key words: melanogenesis; melanin; melanoma; tyrosinase; gamma radiation Melanoma is the tumor with the most rapidly increasing incidences worldwide and it is predicted that by 2010, 1 person out of 50 white persons will be affected by this disease.1 Surgical excision is an effective treatment for early-stage melanomas (localized to the skin), and it is widely accepted that melanoma is resistant to all therapeutic modalities once the metastatic process started. 1-4The use of radiotherapy for advanced melanoma is controversial, and it serves mainly as palliative treatment. [5][6][7][8][9] Most likely the radioresistance of melanoma is due to the presence of melanin pigment, which acts as endogenous radioprotector. 10,11The major role of cutaneous melanin is protection against the harmful actions of solar radiation, by acting as a filter against ultraviolet radiation (UVR), preventing its penetration and genotoxicity (formation of UV-induced DNA dimmers).11-16 Melanin also neutralizes reactive oxygen species (ROS) generated mostly by UVA, through its antioxidative and free-radical scavenging actions. 13,16,17 Overall, melanin protects against epidermal carcinogenesis or melanomagenesis. 11,12,14,16 Nevertheless, the same positive capacity of melanin to scavenge free radical and ROS becomes undesirable in the response of melanoma to radio-, photo-or chemotherapy 11,16,[18][19][20] ; furthermore, the pro-oxidant properties of melanin can, in certain conditions, stimulate melanoma progression. 21Melanotic and amelanotic melanomas differ in their sensitivity to...

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Section: Discussionmentioning

confidence: 62%

Inhibition of melanogenesis as a radiation sensitizer for melanoma therapy

Brożyna¹,

VanMiddlesworth²,

Slominski³

2008

Intl Journal of Cancer

119

113

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“…Both transplantable melanoma lines were described by Bomirski in 1977 as melanotic (Ma) and amelanotic (Ab) melanoma lines [22,23]. Loss of pigment in the Ab line was accompanied by changes in many biological features -faster tumour growth rate, shorter animal survival time, cell ultrastructure changes and changes in antigenicity and immunogenicity [21,22]. Once established, these melanomas possessed a considerable degree of phenotypic stability over decades of passaging [21].…”

Section: Melanotic Melanoma Line (Ma)mentioning

confidence: 99%

“…Loss of pigment in the Ab line was accompanied by changes in many biological features -faster tumour growth rate, shorter animal survival time, cell ultrastructure changes and changes in antigenicity and immunogenicity [21,22]. Once established, these melanomas possessed a considerable degree of phenotypic stability over decades of passaging [21]. Since their discovery, each melanoma line is maintained in vivo by consecutive, subcutaneous transplantations of tumour material every 21 (Ma) or 11 (Ab) days.…”

Section: Melanotic Melanoma Line (Ma)mentioning

confidence: 99%

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Fas and FasL expression on cells of two transplantable melanoma lines according to their different biological properties.

Zielińska

Kozłowska²,

Cichorek³

et al. 2008

Folia Histochem Cytobiol.

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Abstract. Fas and FasL interaction induces apoptotic cell death. In immunocompetent cells it plays a crucial role in the effector functions of the cells and in the regulation of host immune response. In tumours (e.g. melanoma), FasL expression possibly counteracts the Fas-positive effector T cells that infiltrate into tumours, and consequently the Fas/FasL interaction can contribute to the escape of tumour cells from the systemic immune response. In this study we examined differences in Fas and FasL expression on cells from the hamster melanotic melanoma line (Ma) and a more aggressive amelanotic melanoma line (Ab). We also tried to find out whether the Fas/FasL expression induces an ability to undergo spontaneous apoptosis in these two transplantable melanoma lines. Our previous studies have shown that cells of the Ma line have a higher ability to undergo spontaneous apoptosis than cells of the Ab line. Isolated transplantable melanoma cells were incubated for 4 and 24 hours and after that time the expression of Fas and FasL was estimated by flow cytometry. The results show that there was no Fas expression, although FasL was detected on both melanoma cell lines. Therefore the data reported by other authors indicate that a lack or a low level of Fas expression and an ectopic expression of FasL on melanoma cells can be an escape mechanism of the tumour, to avoid host immune responses. The content of FasL-positive melanotic melanoma cells was higher than in amelanotic melanoma cells and increased with the prolongation of the incubation time. FasL expression on amelanotic melanoma cells was detected after 24 hours at a level similar to that on melanotic melanoma cells after 4 hours incubation time. FasL expression on melanoma cells can induce apoptosis in cytotoxic T lymphocytes and NK cells which are responsible for tumour cells elimination. The results obtained suggest that the Fas/FasL system does not play any significant role in spontaneous apoptosis of two melanoma cell lines. But these results may indicate the presence of immune privilege of tumour cells with FasL expression.

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“…Tyrosinase protein or its mRNA can be detected even in poorly differentiated amelanotic melanomas, [19][20][21] as documented at the ultrastructural level. 22 The relative abundance of tyrosinase mRNA in some undifferentiated amelanotic melanomas 19 allows its use in PCR techniques as a valuable diagnostic option. 20 The same can be said for the determination of TRP-1, recognised by the commercially available antibody MEL-5, and TRP-2, which acts as dopachrome tautomerase.…”

Section: Discussionmentioning

confidence: 99%

Gene expression profiles of giant hairy naevi

Dasu

Barrow

Hawkins³

et al. 2004

J Clin Pathol

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Background: Congenital neomelanocytic naevi appear in nearly 1% of newborns. Giant hairy naevi (GHN) are uncommon lesions covering large areas of the body. They are of concern because they have the potential to transform into malignant melanomas. Aims: To describe gene expression profiles of GHN and nearby normal skin from patients with GHN and normal control skin (from patients with cleft lip/palate). Methods: Tissues from three patients with GHN and two normal controls were studied for differences in gene expression profiles. Total RNA was isolated from normal skin near the hairy naevus, GHN, and skin from normal controls. The RNA samples were subjected to probe labelling, hybridisation to chips, and image acquisition according to the standard Affymetrix protocol. Results: There were 227 genes affected across all samples, as determined by DNA microarray analysis. There was increased expression of 22 genes in GHN compared with nearby normal skin. Decreased expression was noted in 73 genes. In addition, there was increased expression of 36 genes in normal skin near GHN compared with normal control skin, and decreased expression of five genes. Categories of genes affected were those encoding structural proteins, proteins related to developmental processes, cell death associated proteins, transcription factors, growth factors, stress response modulators, and collagen associated proteins. Changes in mRNA expression were checked by reverse transcription polymerase chain reaction. Conclusions: Genetic profiles of GHN may provide insight into their pathogenesis, including their potential for malignant transformation. Such information may be useful in improving the understanding and management of these lesions.

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The natural history of a family of transplantable melanomas in hamsters

Cited by 68 publications

References 118 publications

Inhibition of melanogenesis as a radiation sensitizer for melanoma therapy

Inhibition of melanogenesis as a radiation sensitizer for melanoma therapy

Fas and FasL expression on cells of two transplantable melanoma lines according to their different biological properties.

Gene expression profiles of giant hairy naevi

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