Melanoma Inhibitory Activity

Melanoma Inhibitory Activity

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About Melanoma Inhibitory Activity:

Melanoma inhibitory activity (MIA) was initially identified as an 11 kDa protein that was secreted from malignant melanoma cell. Research has shown that MIA is strongly expressed in melanoma and melanoma cell lines, making it a prognostic marker. It has also been discovered that MIA mRNA expression directly correlates with progressive malignancy of melanocytic tumours.

Disease Relevance
Melanoma inhibitory activity is a protein that acts as a valuable marker in patients with malignant melanoma due to enhanced values that indicate metastatic melanoma stages III and IV. Evidence that has been obtained from in vitro and in vivo experiments show that MIA plays a crucial role in melanoma metastasis and invasion. In neoplastic tissues, MIA expression was detected in malignant melanomas, chondrosarcomas and also a variety of different adenocarcinomas such as breast and colon cancer.

Chemical Compound and Disease Context
Research has suggested that MIA might play a crucial role in tumour progression and also the spread of malignant melanomas via mediating detachment of cells from extracellular matrix molecules. Specific pancreatic cancer cell lines, such as MIA PaCA-2 cells, decreased cytotoxicity of anticancer drugs when they adhered to any of the ECM proteins. The only exception was gemcitabine. Analogues of somatostatin and luteinizing hormone-releasing hormone activate tyrosine phosphatases in MIA PaCa-2 human pancreatic cancer cell line membranes and also inhibit growth.

Biological Context
Research has previously shown that upregulation of MIA occurs on a transcriptional level and involves the high conserved region promoter element. Here, MIA-dependent changes of gene expression after long-term inhibition of MIA expression in the human melanoma cell line HMB2 were studied. Real-time reverse transcription=polymerase chain reaction displayed a downregulation of N-cadherin expression and also a reinduction of E-cadherin expression in the MIA-deficient cell clones. When MIA was present, studies observed enhanced migratory ability of melanocytic cells, induction of melanoma-associated genes and also the inhibition of apoptosis due to anoikis.

Analytical, Diagnostic and Therapeutic Context
In situ hybridization, RT-PCR and Northern Blots revealed broad TANGO expression patterns which contrast to the highly restricted expression patterns previously determined for the other members of the MIA gene family. Results indicate that MIA could also contribute to immunosuppression which is frequently seen in malignant melanomas by inhibiting cellular anti-tumour immune reactions.

Other Interactions
In marathon runners, small changes of CRP, sTNFRII, sIL-6R and MIA were detected. This suggests that COMP and MIA are both potential markers for joint metabolism and/or damage in both disease and sports. Compared to healthy controls, a runner’s baseline serum levels of COMP, MIA, TNF-alpha and sIL-6R were significantly increased.