Evaluation of tyrosinase expression in canine and equine melanocytic tumors

Phillips, Jeffrey; Lembcke, Luis M.; Noltenius, Christina E.; Newman, Shelley J.; Blackford, James T.; Grosenbaugh, Deborah A.; Leard, A. Timothy

doi:10.2460/ajvr.73.2.272

Cited by 28 publications

(22 citation statements)

References 27 publications

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“…In general, tyrosinase expression is tightly controlled both spatially and temporally [21]. In tumor tissue, however, tyrosinase expression appears to be constitutively increased [21][22][23]. Furthermore, gray horses at increased risk of tumor formation (ADE Â 2) would be expected to have elevated tyrosinase expression in their melanocytes due to enhanced signaling from the MC1R pathway [18,21,24].…”

Section: Introductionmentioning

confidence: 97%

Development of Immunologic Assays to Measure Response in Horses Vaccinated with Xenogeneic Plasmid DNA Encoding Human Tyrosinase

Lembcke¹,

Kania²,

Blackford³

et al. 2012

Journal of Equine Veterinary Science

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Section: Introductionmentioning

confidence: 97%

Development of Immunologic Assays to Measure Response in Horses Vaccinated with Xenogeneic Plasmid DNA Encoding Human Tyrosinase

Lembcke¹,

Kania²,

Blackford³

et al. 2012

Journal of Equine Veterinary Science

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“…Tyrosinase expression in human melanoma cell lines is variable, thus leading Chen and colleagues to propose that tumours with low levels of tyrosinase expression are poor targets of tyrosinase-specific immunotherapy (Chen et al, 1995). In contrast, a CMM study revealed strong tyrosinase and MHCI mRNA expression in all tumours evaluated irrespective of the degree of tumour pigmentation (Phillips et al, 2012). It should be noted, however, that although these mRNA data are supportive of active gene transcription, one could not conclude that the encoded proteins are properly translated, proteolytically processed and correctly oriented within the cell, which is of key importance to effective antigen presentation (York and Rock, 1996).…”

Section: Possible Immunological Reasons For Lack Of Efficacymentioning

confidence: 99%

Cancer immunology and canine malignant melanoma: A comparative review

Atherton

Morris

McDermott

et al. 2016

Veterinary Immunology and Immunopathology

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Canine melanoma as a model of human melanomaFor at least two decades, veterinary oncologists have advocated using spontaneously occurring tumours in companion animals as models for human cancer (Knapp and Waters, 1997;MacEwen, 1990). Several recent reviews have readdressed this approach identifying osteosarcoma, mammary tumours, head and neck cancers, bladder carcinomas, non-Hodgkin lymphoma, prostatic carcinoma, lung cancer and pertinently oral canine malignant melanoma (CMM) as good models for human neoplasms (Hansen and Khanna, 2004;Khanna and Hunter, 2005;Paoloni and Khanna, 2008). The major benefits of dogs as tumour models include the ability to study genetically outbred and immunologically intact animals in which cancers develop spontaneously and thus, more likely reflect the process of tumourigenesis compared to experimentally-induced neoplasms. As pets and owners share the same environment, they may be exposed to the same carcinogens, which, in part, drive tumour development. Regarding disease modelling, animal tumours often have similar clinical presentation, tumour biology and histopathological appearance to their human counterparts and usually progress more rapidly, thereby shortening data maturation times. In addition, few "standard of care" therapies exist for dogs meaning that within reason, trial therapeutics can be instigated at any point. Given these benefits, companion animal tumour models more accurately reflect the features of human cancers compared to rodent models with CMM being a desirable example of one such neoplasm. Conversely, the opportunity to translate the potential value of state of the art human therapeutics to the veterinary clinic also exists. Oral canine malignant melanoma (CMM) is a spontaneously occurring aggressive tumour with relatively few medical treatment options, which provides a suitable model for the disease in humans. Historically, multiple immunotherapeutic strategies aimed at provoking both innate and adaptive anti-tumour immune responses have been published with varying levels of activity against CMM. Recently, a plasmid DNA vaccine expressing human tyrosinase has been licensed for the adjunct treatment of oral CMM. This article reviews the immunological similarities between CMM and the human counterpart; mechanisms by which tumours evade the immune system; reasons why melanoma is an attractive target for immunotherapy; the premise of whole cell, dendritic cell (DC), viral and DNA vaccination strategies alongside preliminary clinical results in dogs. Current "gold standard" treatments for advanced human malignant melanoma are evolving quickly with remarkable results being achieved following the introduction of immune checkpoint blockade and adoptively transferred cell therapies. The rapidly expanding field of cancer immunology and immunotherapeutics means that rational targeting of this disease in both species should enhance treatment outcomes in veterinary and human clinics.

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“…1,4,16,24,27 In horses, S100 protein is the marker consistently expressed in melanocytic neoplasms. 22 Tyrosinase expression has been detected by immunohistochemistry or molecular methods in equine melanomas, 11,23 but benign equine melanocytic tumors apparently do not express tyrosinase. 23 Monoclonal antibody HMB-45, which recognizes the melanocytic differentiation antigen gp 100, is also expressed in equine malignant melanomas.…”

mentioning

confidence: 99%

Immunohistochemical Expression of Melanocytic Antigen PNL2, Melan A, S100, and PGP 9.5 in Equine Melanocytic Neoplasms

et al. 2013

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The immunoreactivity of PNL2, Melan A, and protein gene product (PGP) 9.5 was compared with that of S100 protein in 50 formalinfixed, paraffin-embedded equine melanocytic neoplasms. PNL2, PGP 9.5, and S100 protein were detected in all 50 neoplasms; none expressed Melan A. PNL2 was not expressed in 62 nonmelanocytic tumors (equine sarcoids, schwannomas, carcinomas, sarcomas, endocrine tumors, sex-cord stromal tumors, germ cell tumors, and leukocytic tumors) or in normal tissues other than epidermis. In summary, antibody PNL2 is a sensitive marker of equine melanocytic neoplasms and is more specific than S100 protein or PGP 9.5. In contrast, the monoclonal antibody to Melan A did not react with any of the equine melanomas.

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Evaluation of tyrosinase expression in canine and equine melanocytic tumors

Cited by 28 publications

References 27 publications

Development of Immunologic Assays to Measure Response in Horses Vaccinated with Xenogeneic Plasmid DNA Encoding Human Tyrosinase

Development of Immunologic Assays to Measure Response in Horses Vaccinated with Xenogeneic Plasmid DNA Encoding Human Tyrosinase

Cancer immunology and canine malignant melanoma: A comparative review

Immunohistochemical Expression of Melanocytic Antigen PNL2, Melan A, S100, and PGP 9.5 in Equine Melanocytic Neoplasms

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