Expression and activity of P-glycoprotein in transplantable hamster melanomas

• Published in: Archives of Dermatological Research Vol. 292; no. 7; pp. 354 - 361
• Main Authors: WITKOWSKI, J. M, KOZŁOWSKA, K, ZARZECZNA, M
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.07.2000
• Subjects: Animals; ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism; Biological and medical sciences; Blotting, Western; Cricetinae; Dermatology; Flow Cytometry; Lymphocytes, Tumor-Infiltrating - metabolism; Lymphocytes, Tumor-Infiltrating - pathology; Medical sciences; Melanoma, Amelanotic - metabolism; Melanoma, Amelanotic - pathology; Melanoma, Amelanotic - secondary; Melanoma, Experimental - metabolism; Melanoma, Experimental - pathology; Melanoma, Experimental - secondary; Mesocricetus; Neoplasm Transplantation; Skin Neoplasms - metabolism; Skin Neoplasms - pathology; Tumors of the skin and soft tissue. Premalignant lesions; Skin disease; Rodentia; P Glycoprotein; Malignant tumor; Potential; Vertebrata; Phenotype; Mammalia; Animal; T-Lymphocyte; Malignant melanoma; Metastatic; Experimental tumor; Hamster
• ISSN: 0340-3696; 1432-069X
• DOI: 10.1007/s004030000146

In the study described here we investigated the possibility of an association between the aggressiveness of melanoma and multidrug resistance phenotype by analyzing the expression and activity of P-glycoprotein (Pgp) in two genetically related transplantable hamster melanomas--a melanotic (Ma) and an amelanotic (Ab) form --which differed in aggressiveness and metastatic potential. Flow cytometric analysis of Pgp activity (using a verapamil-sensitive rhodamine R123 exclusion test) as well as Western blotting of cellular lysates showed its preferential (although not very marked) expression in the Ab melanoma cells. The Ab melanoma cells also exhibited a higher proportion of tumor-infiltrating lymphocytes (TIL), mostly of T cell phenotype, that may have reflected a higher immunogenicity of the tumor. In conclusion, Pgp activity appeared to be associated with less-differentiated more aggressively metastasizing melanoma (the Ab variant) although its role in maintaining this phenotype remains to be established.