A study of the role of gp90 in organ-specificity of metastasizing murine melanoma cells
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Date
1984
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Abstract
The role of a surface glycoprotein with a molecular weight of 90,000 (gp90) in determining organ-specificity of metastasizing murine B16 melanoma cells was studied using gp90-specific rabbit antiserum. The specificity of the antiserum was demonstrated by 2-dimensional sodium dodecyl sulfate:polyacrylamide electrophoresis followed by autoradiography of immunoprecipitates of radiolabeled cell membrane lysates of B16 melanoma cells. The antiserum contained antibodies directed against a cell surface protein on B16 melanoma cells with an approximate 90 kilodalton (KD) molecular weight and a pI of 3.5 to 4.5. In one experiment a surface protein with an approximate molecular weight of 180KD coprecipitated with a 90KD protein. Pretreatment of a brain-colonizing subline of B16 melanoma cells with F(ab')(,2) antibody fragments prepared from the gp90-specific rabbit antiserum did not block experimental metastasis to brain in an in vivo experimental metastasis assay. However, there was a statistically significant increase in the number of animals with ovarian experimental metastases in the experimental group compared to the control group. The distribution of gp90 in normal adult tissues was limited to glandular epithelial cells of the endocrine pancreas, anterior pituitary, adrenal medulla, lacrimal gland, sebaseous glands, stomach, duodenum, perifollicular stromal cells of the ovary, and hepatocytes. A large amount of gp90 was found in the gut epithelium of late gestation fetuses but this antigen was absent in early gestation fetuses. Expression of gp90 was demonstrated in all B16 melanoma cell variants tested, but in variable density. In addition, gp90 was variably expressed on established tumor cell lines of different histologic and species origin, being most consistent on melanoma and lymphoma cell lines. The results of this study indicate that gp90 is: (1) a cell surface protein of cellular origin with a pI of 3.5 to 4.5, (2) expressed late in fetal development, (3) expressed on some adult endocrine and certain mesodermal derived tissues that may be related functionally or embryologically, (4) express on all B16 melanoma variants, but with variable density and, (5) distributed in adult mouse tissues in a pattern very similar to the transferrin receptor in adult human tissues; but is not a tissue- or species-specific antigen nor is it directly or solely responsible for B16 cell localization in organ-specific metastasis.
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Typescript (photocopy).
Keywords
Veterinary Pathology