title: Macrophage inhibitory cytokine-1 is overexpressed in malignant melanoma and is associated with tumorigenicity.
abstract: The incidence of malignant melanoma has increased dramatically over the past four decades. Metastatic melanoma is associated with poor prognosis, as the current treatments do not have a significant impact on prolonging survival or decreasing mortality. We have identified a member of the transforming growth factor-beta superfamily, macrophage inhibitory cytokine (MIC)-1, which is highly expressed in melanoma cells. Of 53 melanoma cell lines that were examined for relative MIC-1 expression by western blot analysis, 35 (66%) showed significantly higher levels of MIC-1 compared to normal melanocytes. Primary melanoma biopsies (15 of 22) were found to contain cells expressing low levels of MIC-1 as determined by immunohistochemistry. In contrast, all metastatic melanoma biopsies examined (16 of 16) had strong expression of MIC-1. Expression of MIC-1 was found to be dependent on the mitogen-activated protein kinase pathway, and is a transcriptional target of the microphthalmia-associated transcription factor. Knockdown of MIC-1 expression using stable short-hairpin RNA in three melanoma cell lines showed a significant decrease in tumorigenicity (P<0.0001). These results indicate that MIC-1 may function to promote development of more aggressive melanoma tumors. MIC-1 may be suitable for development as a serum diagnostic and is a possible target for the treatment of metastatic melanoma.
authors.affiliation: Melanoma Genomics Group, Queensland Institute of Medical Research, Brisbane, Queensland, Australia. Glen.Boyle@qimr.edu.au
authors.forename: Glen M
authors.initials: GM
authors.lastname: Boyle
authors.forename: Julie
authors.initials: J
authors.lastname: Pedley
authors.forename: Adam C
authors.initials: AC
authors.lastname: Martyn
authors.forename: Kelly J
authors.initials: KJ
authors.lastname: Banducci
authors.forename: Geoffrey M
authors.initials: GM
authors.lastname: Strutton
authors.forename: David A
authors.initials: DA
authors.lastname: Brown
authors.forename: Samuel N
authors.initials: SN
authors.lastname: Breit
authors.forename: Peter G
authors.initials: PG
authors.lastname: Parsons