Biochemical characterization of a new melanoma model ??? the minipig MeLiM strain

Abstract

Hereditary minipig melanomas, which have many histopathological and other features in common with their human counterparts, have recently become preferred melanoma models. The MeLiM (Melanoma-bearing Libĕchov Minipig) strain was selected by partial inbreeding. A high tumour incidence and malignant behaviour on the one hand together with the occurrence of spontaneous regression and high susceptibility to the devitalization technique as a new strategy in melanoma therapy, make the MeLiM strain a superior melanoma model to other hereditary swine melanomas. Biochemical analyses of the tumours revealed: (i) a high concentration of eumelanin and low concentration of phaeomelanin in melanoma cells, which makes the probability of photochemical regression of MeLiM melanomas negligible; (ii) an extremely high level of melanosomes (almost half of the melanoma dry weight), which suggests a high differentiation of the MeLiM melanoma and is consistent with its mechanical rigidity; (iii) the presence of typical melanoma enzymes--tyrosinase, alpha-mannosidase and gamma-glutamyltransferase; and (iv) in the tumours regressing as a consequence of devitalization treatment, alpha-mannosidase activity was reduced and tyrosinase activity approached the detection threshold, which is in accordance with the substitution of melanoma tissue for connective tissue in devitalized tumours observed histologically. (Immuno)histochemical comparisons (based on dopaoxidase reaction, S100 and HMB-45 reactivities) of the skin from white and pigmented minipigs revealed the absence of melanocytes in white skin. This is the first direct evidence supporting a possible explanation for the absence of melanoma in white minipigs. The similarities and dissimilarities of the MeLiM model compared with human melanoma are highlighted.

Utilizing of Adsorptive Transfer Stripping Technique Brdicka Reaction for Determination of Metallothioneins Level in Melanoma Cells, Blood Serum and Tissues

“…A high tumour incidence (in 57% of animals), typical progressive growth (about 34% animals die usually within the first 2 months of age), development of metastases in distant organs, and the existence of various multiple pigment lesions (naevi, superficial spreading melanoma and nodular melanoma) make the MeLiM strain a good model of human disease [82,84-89]. …”

Spatial mapping of metals in tissue-sections using combination of mass-spectrometry and histology through image registration

“…The MeLiM ( Me lanoma-bearing Li bechov Mi nipig) strain of miniature pigs with heritable cutaneous melanoma is an original animal cancer model with histopathological, biochemical and molecular biological similarities to human melanoma6789. Multiple skin melanomas appear at birth or shortly thereafter in approximately half of all piglets.…”

Germline gene polymorphisms predisposing domestic mammals to carcinogenesis

“…The contribution of particular breeds in the MeLiM pigs, depending on the family is: Sinclair 34-53%, Goettingen 19-34%, Vietnamese 10-18%, Landrace 3-7%, Cornwall 1-6% and Large White 0-6%. 33 Both SSCM and MeliM mini pigs have been extensively studied to identify susceptibility loci for heritable melanoma and loci associated with melanoma regression. Combined studies of classical breeding and complex segregation analysis in SSCM pigs revealed two loci associated with melanoma initiation and tumour penetrance.…”