Expression of gp185HER-2 in human cutaneous melanoma: implications for experimental immunotherapeutics.
Over-expression of the HER-2 oncogene correlates with poor prognosis in breast and ovarian carcinomas. Using a sensitive immunohistochemical assay, we have detected low levels of gp185HER-2 in intradermal nevi (78%) and in primary (75%) and metastatic melanomas (58%). The HER-2 gene product expressed by cultured melanoma cells had the expected molecular weight, but no levels of tyrosine phosphorylation could be detected. Consistently, we were unable to inhibit in vitro growth of melanoma cells with an anti-gp 185HER-2 MAb, in conditions in which the growth of SKBr-3 breast-carcinoma cells was severely impaired. However, immunotoxins to gp 185HER-2 were able to kill gp185HER-2-positive melanoma cells. These data indicate that low levels of gp185HER-2 are expressed by the melanocyte lineage, with no correlation with transformation or tumor progression. Nevertheless, gp185HER-2 appears a suitable target for immunotherapy of cutaneous melanoma.
Natali
P G
PG
Regina Elena Cancer Institute, Rome, Italy.
Nicotra
M R
MR
Digiesi
G
G
Cavaliere
R
R
Bigotti
A
A
Trizio
D
D
Segatto
O
O
D000818:Animals; D000911:Antibodies, Monoclonal; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity; D015153:Blotting, Western; D001943:Breast Neoplasms; D002455:Cell Division / Q000187:drug effects; D005134:Eye Neoplasms / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy; D000922:Immunotoxins / Q000633:toxicity; D008545:Melanoma / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D051379:Mice / Q000276:immunology; D009699:N-Glycosyl Hydrolases; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009856:Oncogene Proteins, Viral / Q000032:analysis* / Q000096:biosynthesis; D009857:Oncogenes; D010940:Plant Proteins / Q000633:toxicity; D018719:Erb-b2 Receptor Tyrosine Kinases; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000972:Antineoplastic Agents, Phytogenic; D000922:Immunotoxins; D009699:N-Glycosyl Hydrolases; D009856:Oncogene Proteins, Viral; D010940:Plant Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins