Ganglioside antigens in tissue sections of skin, naevi, and melanoma — Implications for treatment of melanoma

Hersey, Peter

doi:10.1007/978-1-4615-3938-4_8

Cited by 21 publications

(6 citation statements)

References 37 publications

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“…Both normal skin melanocytes and nevus cells express mRNA for high-affinity FGF receptors and are responsive to FGF-2 in vitro Pigment cells were cultured both from normal human skin and from human nevocellular nevi as described in Materials and Methods. The cultures were confirmed to be 100% melanocytes by immunostaining with antibodies against S-100 and ganglioside GD3 (data not shown), which are widely used as markers for melanocytes and melanocyte neoplasms (Stefansson et al, 1982;Hersey, 1991;Barrett and Raha, 1997).…”

Section: Resultsmentioning

confidence: 84%

FGF Expression Allows Nevus Cells to Survive in Three-Dimensional Collagen Gel Under Conditions that Induce Apoptosis in Normal Human Melanocytes

Alanko

Rosenberg

Saksela

1999

Journal of Investigative Dermatology

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Melanocytes, the pigment forming cells of the skin, form an almost nonproliferating cell population located to the lowermost part of the epidermis. Normally melanocytes are not found higher in the epidermis or in the dermis. Nevi consist of melanocytes with altered growth characteristics and localization. The common pigmented nevus, a benign skin lesion, develops when melanocytes proliferate in the dermo-epidermal junction or in the dermis. Here we report growth characteristics of in vitro cultured normal human melanocytes and dermal nevus-derived melanocytes. As previously reported, nevus cells have a moderate to high FGF-2 expression level. Here we demonstrate that dermal nevus cells are able to survive in three-dimensional type 1 collagen culture, while normal human melanocytes rapidly undergo apoptosis. Melanocytes also, however, survive in collagen cultures in the presence of exogenous FGF-2. The survival of nevus cells in collagen is suppressed by protamine, an inhibitor of FGF-mediated cell stimulation. The in vivo growth environment of dermal nevus cells consists largely of type I and type III collagens. The results suggest that FGF-2 expression by nevus cells allows them to adapt to grow in the dermis. FGF-2 obviously has importance as a melanocyte survival factor and probably also in the development of malignant melanoma.

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Section: Resultsmentioning

confidence: 84%

FGF Expression Allows Nevus Cells to Survive in Three-Dimensional Collagen Gel Under Conditions that Induce Apoptosis in Normal Human Melanocytes

Alanko

Rosenberg

Saksela

1999

Journal of Investigative Dermatology

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“…It is also expressed abundantly in retinoblastoma tumour cells, so it was used as a suitable marker for identification of suspicious tumour cells in the bone marrow or cerebrospinal fluid of affected patients (Seeger 2011;Laurent et al 2013). However, low levels of GD2 expression in some normal tissues such as the peripheral nerves, neurons (Mennel et al 1992), skin melanocytes (Hersey 1991) and bone marrow stem cells (Rasini et al 2013) limit the widespread use of this antigen for delivering targeted therapy to the eye because of anticipated toxicity, as evident when used for immunotherapy of neuroblastoma (Sorkin et al 2010).…”

Section: Introductionmentioning

confidence: 99%

Immunoreactivity of the 14F7 Mab raised against N‐Glycolyl GM3 Ganglioside in retinoblastoma tumours

Torbidoni

Scursoni

Camarero

et al. 2014

Acta Ophthalmologica

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ABSTRACT.Introduction: The identification of molecules expressed selectively on the surface of retinoblastoma cells would allow applying targeted therapies. The Ganglioside, N-Glycolyl-GM3 (NeuGc-GM3), is an attractive candidate, as it has been detected in other paediatric neuroectodermic tumours, and it is not expressed in human normal tissues. The 14F7 antibody recognizes specifically the ganglioside NeuGc-GM3. Purpose: To characterize the expression of NeuGc-GM3 in retinoblastoma cell lines and in retinoblastoma tumours using the 14F7 monoclonal antibody. Methods: We studied WERI-Rb1 and Y79 cell lines, 24 retinoblastoma primary tumours from unilateral and bilateral cases and two bone marrow biopsies from metastatic retinoblastoma. Tumours were classified into three groups: non-invasive (n = 13), invasive (n = 9) and metastatic (n = 2). Three eyes enucleated because of non-tumoural conditions were used as controls. Cell lines and tumour sections were studied by immunohistochemistry using the 14F7 antibody. NeuGc-GM3 expression was evaluated by analysing the percentage of positive tumoural cells and the staining intensity. These parameters were analysed comparatively among the three groups. Results: Both retinoblastoma cell lines showed immunoreactivity to NeuGc-GM3 but WERI-Rb1 presented higher intensity than Y79. All the tumours studied showed strong immunoreactivity to NeuGc-GM3 with no significant differences among groups. In both bone marrow specimens, NeuGc-GM3 immunoreactivity was observed in retinoblastoma cells. In bilaterally enucleated cases, NeuGc-GM3 immunoreactivity was not altered before and after chemotherapy. Non-tumoural retinas were negative. Conclusions: NeuGc-GM3 is highly expressed in retinoblastoma cell lines, tumours and metastatic cells to the bone marrow, and it is not detectable in control eyes. There were no significant differences in the immunoreactivity to 14F7 among tumours from different disease stages. Its immunoreactivity did not change after chemotherapy.

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“…Gangliosides are present on melanoma cells and some nonneoplastic cells [84], and have been found to be effective targets for active immunotherapy [85][86][87]. A randomized trial comparing adjuvant therapy of node-positive melanoma with BCG to treatment with BCG plus purified GM2 ganglioside resulted in an 18% improvement in disease-free survival and an 11% improvement in overall survival in the treatment group, although neither result was statistically significant [88].…”

Section: A) Ganglioside Vaccinesmentioning

confidence: 99%

Vaccine Therapy of Melanoma: An Update

Demierre¹,

Swetter²,

Sondak³

2005

CCTR

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Objective: To review recent epidemiologic studies of vaccination and melanoma risk as well as critically discuss the different melanoma vaccines under investigation in multicenter phase III melanoma vaccine trials.Data Sources: A retrospective review of the literature.Study Selection: Studies included those on the risk of melanoma and vaccination, historically relevant data, and ongoing or recently published phase III melanoma vaccine trials. The referenced study designs and methodologies varied.Data extraction and Synthesis: 3 reviewers extracted Data and the main results are presented in a quantitative descriptive manner.Conclusion: Vaccine therapy of melanoma remains promising, given the associated low toxicity. Epidemiologic studies suggest a role for vaccines against certain infectious diseases in melanoma prevention. While results of ongoing phase III melanoma vaccines trials may open new avenues for disease prevention, a better understanding of immune responses to melanoma vaccines will be necessary.

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Ganglioside antigens in tissue sections of skin, naevi, and melanoma — Implications for treatment of melanoma

Cited by 21 publications

References 37 publications

FGF Expression Allows Nevus Cells to Survive in Three-Dimensional Collagen Gel Under Conditions that Induce Apoptosis in Normal Human Melanocytes

FGF Expression Allows Nevus Cells to Survive in Three-Dimensional Collagen Gel Under Conditions that Induce Apoptosis in Normal Human Melanocytes

Immunoreactivity of the 14F7 Mab raised against N‐Glycolyl GM3 Ganglioside in retinoblastoma tumours

Vaccine Therapy of Melanoma: An Update

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