Disease relevance of MIA

• Melanoma inhibitory activity (MIA) protein is a clinically valuable marker in patients with malignant melanoma, as enhanced values diagnose metastatic melanoma stages III and IV [1].
• Evidence obtained from in vitro and in vivo experiments indicated that MIA plays an important functional role in melanoma metastasis and invasion [2].
• In neoplastic tissues MIA expression was detected in malignant melanomas, in chondrosarcomas and less frequently in a variety of different adenocarcinomas including breast and colon cancers [2].
• METHODS: MIA serum concentrations of patients with different rheumatic diseases were examined and compared with healthy individuals and malignant melanoma patients [3].
• MIA is secreted into the culture supernatant by several malignant melanoma cell lines as an M(r) 11,000 autocrine growth factor and acts as a potent tumor cell growth inhibitor for malignant melanoma cells and some other neuroectodermal tumors, including gliomas [4].

Psychiatry related information on MIA

• Although the combined impact of MIA complications seems to determine the extremely poor clinical outcome in the ESRD patients, there are significant unexplained individual differences in the development of the MIA syndrome, implying that genetic differences might play a role [5].

High impact information on MIA

• Positivity for MIA (i.e., immunohistologic staining by MIA-15-5, which defines H/Le(y)/Le(b) antigens) is inversely correlated with survival among patients with primary lung cancer and may be of prognostic value [6].
• The growth-inhibiting peptide hormone somatostatin stimulates phosphotyrosine phosphatase activity in the human pancreatic cell line MIA PaCa-2 [7].
• Comparative effects of selected drug combinations on the growth of a human pancreatic carcinoma cell line (MIA PaCa-2) [8].
• The exposure of MIA PaCa-2 cells to 1.6 X 10(-5) M 5-fluorouracil (FUra) followed by 2 X 10(-8) M DHAD or 3 X 10(-7) M ADR had an additive (with DHAD) or synergistic (with ADR) effect when the two drugs were given simultaneously and a synergistic effect with either drug when they were given 2, 6, or 24 hours apart [8].
• METHODS: We measured apoptosis and necrosis, caspase activation, and mitochondrial dysfunction in MIA PaCa-2 and PANC-1 pancreatic carcinoma cells both detached and attached to ECM proteins [9].

Chemical compound and disease context of MIA

• These findings also suggest that MIA may play a role in tumor progression and the spread of malignant melanomas via mediating detachment of cells from extracellular matrix molecules by modulating integrin activity [10].
• Pancreatic cancer cell lines, especially MIA PaCa-2 cells, adhering to any of the ECM proteins showed decreased cytotoxicity of anticancer drugs, except for gemcitabine [11].
• Analogues of somatostatin (SS) and luteinizing hormone-releasing hormone (LH-RH) activate tyrosine phosphatases in MIA PaCa-2 human pancreatic cancer cell line membranes and inhibit growth [12].
• To determine whether inhibition of NQO(1) would alter the malignant phenotype, MIA PaCa-2 pancreatic cancer cells were treated with a selective inhibitor of NQO(1), dicumarol [13].
• Reversion of transcriptional repression of Sp1 by 5 aza-2' deoxycytidine restores TGF-beta type II receptor expression in the pancreatic cancer cell line MIA PaCa-2 [14].

Biological context of MIA

• We have previously shown that upregulation of MIA occurs on a transcriptional level and involves the highly conserved region (HCR) promoter element [15].
• Here, MIA-dependent changes of gene expression after long-term inhibition of MIA expression in the human melanoma cell line HMB2 were investigated [16].
• Real-time reverse transcription-polymerase chain reaction (RT-PCR) showed a downregulation of N-cadherin expression and a reinduction of E-cadherin expression in the MIA-deficient cell clones [16].
• In the presence of MIA, we observed enhanced migratory ability of melanocytic cells, induction of melanoma-associated genes as well as inhibition of apoptosis due to anoikis [16].
• Structural homology of MIA with the binding sites of alpha4beta1 integrin results in complex interactions of MIA with molecules binding to alpha4beta1 integrin [17].

Anatomical context of MIA

• Specific expression and regulation of the new melanoma inhibitory activity-related gene MIA2 in hepatocytes [18].
• As all these molecules are associated with migration, the effect of MIA on migration of human primary melanocytes was analysed [16].
• Here we describe the effects of MIA on the activation of human PBMCs and auto-/allogeneic lymphokine-activated killer cell (LAK) cytotoxicity in human MIA-negative glioma cell lines and MIA-positive melanoma cell lines in vitro [17].
• As cells of the immune system express alpha4beta1 integrins (VLA-4), we investigated whether MIA may modulate the function of human leukocytes [17].
• As MIA is not only produced by melanoma cells, but also by differentiated chondrocytes, we examined whether serum levels of MIA are correlated with inflammation and/or joint destruction in rheumatic diseases [3].

Associations of MIA with chemical compounds

• The structure also suggests a likely protein interaction site and suggests that, unlike conventional SH3 domains, MIA does not recognize polyproline helices [19].
• In vivo, ZD6474 showed significant antitumor activity alone and in combination with radiotherapy and gemcitabine, and the combination of all three modalities enhanced MIA PaCA-2 tumor growth inhibition compared with gemcitabine alone [20].
• Compared with the expression of pMel (HMB-45), tyrosine, and S-100 in these tumours, these results show that MIA provides a novel and sensitive marker for neoplastic melanocytes [21].
• Moreover, S100beta and MIA were not superior to the conventional parameters lactate dehydrogenase and C-reactive protein (CRP) on multiple logistic regression analysis [22].
• Constitutively activated STAT3 was also found in pancreatic tumor cell lines (Panc-1 and MIA PaCa-2) which could be modulated by indole-3-carbinol (13C) and genistein [23].

Physical interactions of MIA

• MIA is a potent melanoma detachment factor that interferes with cellular adherence by binding to fibronectin and laminin, blocking their interaction with alpha4beta1 and alpha5beta1 integrins [24].

Regulatory relationships of MIA

• Expression of a STAT3 dominant negative prevented SFM-stimulated cell proliferation of MIA PaCa-2 cells, suggesting that activation of STAT3 by ErbB2 is required for a growth factor-independent phenotype of these cells [25].
• PURPOSE: Monitoring advanced malignant melanoma, serum levels of S100-beta (S100beta) and melanoma-inhibiting activity (MIA) were assessed for the ability to discriminate progressive from nonprogressive disease [26].
• Here, we show that MIA negatively regulates the activity of the mitogen-activated protein kinase pathway in malignant melanoma [10].
• OSR1 mRNA was significantly up-regulated in a pancreatic cancer cell line MIA PaCa-2, and was weakly expressed in gastric cancer cell lines OKAJIMA, MKN45, pancreatic cancer cell lines PANC-1, BxPC-3, AsPC-1, PSN-1, Hs766T, and esophageal cancer cell line TE10 [27].
• In an assay of anchorage-independent growth, exogenous FGF-2 stimulated a maximum 15-fold and 10-fold increase in colony formation by the cell lines MIA PACA-2 and PANC-I respectively [28].

Other interactions of MIA

• Only modest changes of CRP, sIL-6R, sTNFRII and MIA occurred during the run [29].
• Thus, our data suggest that COMP and MIA are markers for distinct aspects of joint metabolism and/or damage in both disease and sport [29].
• RESULTS: Compared with healthy controls, the runner's baseline serum levels of TNF-alpha, sIL-6R, COMP and MIA were significantly increased [29].
• Upregulation of HMG1 leads to melanoma inhibitory activity expression in malignant melanoma cells and contributes to their malignancy phenotype [15].
• Of these rheumatic diseases, a significant increase in MIA serum concentrations was seen only in patients with RA, associated with rheumatoid factor (RF) positivity and joint destruction [3].

Analytical, diagnostic and therapeutic context of MIA

• Interestingly, in situ hybridization, RT-PCR and Northern Blots revealed very broad TANGO expression patterns in contrast to the highly restricted expression patterns previously determined for the other members of the MIA gene family [30].
• Our results indicate that MIA may contribute to immunosuppression frequently seen in malignant melanomas by inhibiting cellular antitumor immune reactions [17].
• We therefore quantitated serum levels of MIA protein by means of a nonradioactive ELISA and investigated whether MIA provides a clinically useful parameter in patients with malignant melanomas [31].
• Here we report the purification and molecular cloning of a novel growth regulating protein, designated melanoma inhibitory activity (MIA) and provide a preliminary functional characterization [4].
• Using far Western blotting and co-immunoprecipitation we searched for MIA-binding cell surface proteins [10].

References