Modulation of the antigenic phenotype of human melanoma cells by differentiation-inducing and growth-suppressing agents.
Tumor cells often display alterations in their normal program of cellular differentiation. A promising approach for the treatment of cancer involves the induction of terminal differentiation and a loss of proliferative capacity in cancer cells. In human melanoma cells, the combination of mezerein (MEZ) and fibroblast interferon (IFN-beta), results in a rapid and irreversible suppression of cell growth with a concomitant increase in the synthesis of melanin. The induction of terminal differentiation is associated with alterations in the expression of several cellular genes, including fibronectin, ISG-15 and ISG-54, and changes in the expression of specific cell surface antigens, including intercellular adhesion molecule-1 (ICAM-1) and HLA Class I antigens. In the HO-1 human melanoma cell line, induction of terminal differentiation by MEZ plus IFN-beta results in an induction and/or increased expression of ICAM-1, HLA Class I antigens and HLA Class II antigens. IFN-beta and MEZ alone can modulate expression of these antigens to a lower extent than does the combination of compounds. Induction of terminal differentiation and the irreversible suppression of cell growth is not a prerequisite for antigenic modulation in HO-1 cells. This is indicated by the inability of immune interferon (IFN-gamma), a strong inducer of ICAM-1, HLA Class I antigens and HLA Class II antigens synthesis, or the combination of IFN-beta plus IFN-gamma which synergistically but reversibly suppresses HO-1 growth, to induce melanin synthesis or terminal differentiation in HO-1 cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Division of Pediatric Hematology/Oncology, Columbia University, College of Physician & Surgeons, New York, NY 10032.
L
L
Guarini
G M
GM
Graham
H
H
Jiang
S
S
Ferrone
S
S
Zucker
P B
PB
Fisher
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004224:Diterpenes; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006680:HLA Antigens / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D016899:Interferon-beta / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology*; D008543:Melanins / Q000096:biosynthesis; D008545:Melanoma / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D010879:Piperazines / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D013729:Terpenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D004224:Diterpenes; D006680:HLA Antigens; D007546:Isoquinolines; D008543:Melanins; D009363:Neoplasm Proteins; D010879:Piperazines; D013729:Terpenes; D018799:Intercellular Adhesion Molecule-1; C011309:mezerein; D016899:Interferon-beta; D007371:Interferon-gamma; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C