File(s) not publicly available

Macrophage inhibitory cytokine-1 is overexpressed in malignant melanoma and is associated with tumorigenicity

journal contribution
posted on 06.12.2017, 00:00 by G Boyle, J Pedley, A Martyn, K Inglis, G Strutton, D Brown, S Breit, P Parsons
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-b 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 (Po0.0001). 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.

Funding

Other

History

Volume

129

Issue

2

Start Page

383

End Page

391

Number of Pages

9

eISSN

1523-1747

ISSN

0022-202X

Location

USA

Publisher

Nature

Language

en-aus

Peer Reviewed

Yes

Open Access

No

Era Eligible

Yes

Journal

Journal of investigative dermatology.

Usage metrics

Exports