Biochemical characterization of a new melanoma model--the minipig MeLiM strain.
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.
Borovanský
Jan
J
Department of Biochemistry and Experimental Oncology and Institute of Inherited Metabolic Diseases, 1st Faculty of Medicine, Charles University, 128 53 Prague 2, Czech Republic. jborov@lf1.cuni.cz
Horák
Vratislav
V
Elleder
Milan
M
Fortýn
Karel
K
Smit
Nico P
NP
Kolb
Adriana M
AM
D000818:Animals; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D006801:Humans; D007150:Immunohistochemistry; D008543:Melanins / Q000378:metabolism; D008544:Melanocytes / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism* / Q000628:therapy*; D020460:Melanosomes / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000378:metabolism; D009418:S100 Proteins / Q000378:metabolism; D013552:Swine; D013556:Swine, Miniature; D014461:Ultracentrifugation; D043323:alpha-Mannosidase / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D008543:Melanins; D009418:S100 Proteins; C016042:phaeomelanin; D014442:Monophenol Monooxygenase; D005723:gamma-Glutamyltransferase; D043323:alpha-Mannosidase