Expression and function of CD9 in melanoma cells.
CD9, a member of the tetraspanin family, functions as an organizer in "tetraspanin webs," through interacting with other cell adhesion molecules. It plays a role in differentiation, fertilization, and cell migration. We investigated the expression and function of CD9 in melanoma. CD9 protein expression in B16 mouse melanoma and six human melanoma cell lines was decreased compared to normal melanocytes. B16F1 clones stably overexpressing CD9 had reduced ability to form colonies in soft agar; however, paradoxically these overexpressing clones had increased ability to invade Matrigel. Similarly, transient overexpression of CD9 in the human metastatic melanoma cell line WM9 dramatically decreased anchorage-independent growth, while transient overexpression of CD9 in the radial growth phase cell line SbCl2 resulted in the gain of Matrigel invasion activity. DNA sequencing of CD9 cDNA from all six human melanoma cell lines did not show deletions, insertions, or mutations. Treatment of all six human melanoma cell lines with the histone deacetylase inhibitor trichostatin A increased CD9 levels. The DNA methylation inhibitor 5-aza-cytidine also increased CD9 protein levels with greater increases seen in cell lines derived from more malignant melanomas.
Department of Biochemistry and Microbiology, Marshall University, Huntington, West Virginia, USA.
Jun
J
Fan
Guo-Zhang
GZ
Zhu
Richard M
RM
Niles
D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D001374:Azacitidine / Q000494:pharmacology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D019175:DNA Methylation / Q000187:drug effects; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D007231:Infant, Newborn; D008544:Melanocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D051379:Mice; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D060245:Tetraspanin 29; D014162:Transfection
D015703:Antigens, CD; C554869:CD9 protein, human; C554870:Cd9 protein, mouse; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D008562:Membrane Glycoproteins; D060245:Tetraspanin 29; C012589:trichostatin A; D001374:Azacitidine