An Animal Model for Human Melanoma

Abstract

Experimental animal models that are directly relevant to human melanoma are lacking. We propose the Angora goat as a potentially useful field model with experimental potential and to this end have examined the prevalence and site distribution of all skin cancers in 28 Angora goat herds in Queensland, Australia. The prevalence of benign melanocytic lesions (lentigines) and their experimental induction by sunlight were also investigated. Among 1731 goats over 2 years of age, 139 malignant skin tumors were excised from 95 affected animals. The prevalence of squamous cell carcinoma (SCC) was 3.8% and of melanoma, 2.2%. Main site of occurrence of melanoma (83%) was the dorsal surface of the ear; in contrast SCC occurred mostly (84%) on the perineum. Lentigines were darker and more prevalent on the exposed compared with the unexposed surface of the ear in Angoras, analogous to the higher prevalence of nevi on the exposed compared with the less exposed inner surface of the arm in humans. Lentigines, which were also found on the perineum though lighter in color than on the dorsal ear, were absent in young animals under 3 months but were numerous in 1-3 year olds. Furthermore in an experimental substudy eight goats, having one flank repeatedly shorn and the contralateral flank left unshorn, revealed consistently more solar lentigines on the shorn flank (P < 0.05) when both sides were examined after 9 months. Histopathological examination of paired skin biopsies from five of these goats also showed more abundant pigmentation in skin from the exposed, as compared with the unexposed flank. These findings indicate that sunlight induces tumors and lentigines in goats in a highly site-specific manner. The Angora goat model may suggest paradigms for explaining the site differences observed for human melanoma and may also be useful in the future clarification of molecular changes following carcinogenic levels of sun exposure.

One Hundred Two Tumors in 100 Goats (1987–2011)

“…The latter is one of the most frequently reported topographic locations for caprine SCC. 4,14,19,34 None of the SCCs in this study occurred on the face and eyelids or in internal organs. Thymoma is one of the more common neoplasms in goats, 19 especially in dairy breeds.…”

“…All melanocytic tumors were malignant, consistent with reported cases. 4,6,14,19 Pheochromocytoma has been reported in goats 11,19,21 but is more common in cattle and dogs. 7 All 3 cases in this cohort were malignant, but invasion of the vena cava was more common than distant metastasis.…”

“…1 Retrospective studies of caprine tumors have been published in the past 40 years, 4,6,10,12,14,19,34 but some had a narrow focus or included few new cases. For example, a 1996 study of cutaneous neoplasms was focused on melanomas and squamous cell carcinomas.…”

“…For example, a 1996 study of cutaneous neoplasms was focused on melanomas and squamous cell carcinomas. 14 Another report primarily on nonneoplastic external masses. 12 Three studies published 30 or more years ago 4,6,10 and a more recent abstract 19 cover a wide spectrum of conditions in a larger number of goats.…”

Ultraviolet Light as a Modulator of Melanoma Development

“…Grey horses and certain strains of pig are models for genetic susceptibility to melanoma, although there is no evidence for any effects of UVR exposure (Rosengren Pielberg et al, 2008;Seltenhammer et al, 2004). Opossom, guinea pigs and Angora goats have also been used as models for melanocytic lesion development (Chan et al, 2001;Menzies et al, 2004;Green et al, 1996). However except for goats, UVR exposure is not known to play any role in melanoma development in these animals.…”