Melanoma-inhibiting Activity Research Articles

Melanoma-inhibiting activity promotes the migration and odontoblastic differentiation of stem cells of apical papilla

ObjectiveMelanoma Inhibitory Activity (MIA) has been predominantly studied in the context of melanoma and cartilage development. However, its role in dental pulp development and stem cell behavior remains largely unexplored. This study investigates the expression pattern of MIA in dental pulp tissues and its potential role in the proliferation, migration, and odontoblastic differentiation of stem cells from the apical papilla (SCAPs). DesignMIA expression in human pulp tissue was demonstrated by immunohistochemistry. SCAPs were cultured in normal and mineralization induction media, with MIA levels monitored via RT-qPCR and Western blot. Cell proliferation was evaluated using the CCK8 assay, while transwell and cell scratch assays were conducted to examine cell migration. The effect of MIA on odontoblastic differentiation was examined by qRT-PCR, Alkaline phosphatase activity assay, and Western blot. siRNA was used to knock down MIA to investigate its effect. A mouse subcutaneous implantation model was used to assess whether MIA promotes odontoblastic differentiation in vivo. ResultsMIA expression was observed in the papilla and odontoblasts layer of the developing pulp. In vitro, MIA expression increased during SCAPs differentiation and was found to significantly enhance migration, and odontoblastic differentiation but not proliferation. Gene knockdown experiments confirmed MIA’s pivotal role in promoting SCAPs migration and differentiation. In vivo, MIA facilitated the formation of dentin-like structures and enhanced pulp-dentin complex regeneration. ConclusionMIA plays a crucial role in SCAPs’ migration and differentiation, suggesting its potential application in pulp-dentin regeneration therapies. Further studies are required to fully elucidate the underlying mechanisms.

Exploring the molecular mechanisms network of breast cancer by multi-omics analysis.

Breast cancer (BC), the most prevalent malignancy in women globally, still lacks comprehensive research on its molecular targets and necessitates further investigation into the underlying molecular mechanisms driving its initiation and progression. The GSE20685 Series Matrix File downloaded from the Gene Expression Omnibus database was divided into a high-risk group (n=49) and a low-risk group (n=278) to construct the co-expression network. Four hub genes were identified based on the Weighted Gene Co-expression Network Analysis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analyses were performed. Hub gene immune infiltration was investigated using the Tumor Immune Estimation Resource database, and CD4+ T cell expression levels were substantially correlated with hub gene expression. Based on the CancerRxGene database (Genomics of Drug Sensitivity in Cancer database), it was found that the hub genes were highly sensitive to common chemotherapy drugs such as AKT inhibitor VIII and Erlotinib. The expression of Secreted Frizzled-Related Protein 1, melanoma-inhibiting activity (MIA), and Keratin 14 was related to tumor mutation burden, and the expression of MIA also affected the microsatellite instability of the tumor. This study employs multi-omics analysis to investigate the molecular network associated with the prognosis of BC, highlighting its intricate connection with the immune microenvironment. These findings pinpoint four crucial genes in BC progression, offering targets for further research and therapy. Their connections to immune infiltration and chemotherapy sensitivity underscore complex interactions in the tumor microenvironment.

Protein and non-protein biomarkers in melanoma: a critical update

Melanoma is the most malignant type of all skin neoplasms. Its worldwide incidence has steadily increased during the past decades, suggesting a probable melanoma 'epidemic'. Although current clinical, morphologic, and histopathologic methods provide insights into disease behavior and outcome, melanoma is still an unpredictable disease. Once in an advanced stage, it remains a disastrous affliction with scarce therapeutic options. Therefore, significant efforts need to be made in finding informative biomarkers or surrogate markers that could aid or improve early diagnosis of melanoma, its correct staging, the discrimination of other pathological conditions as well as indicate patients' prognosis or the most appropriate therapeutic regimes. Ideally these markers are secreted into body fluids and easily amenable to the design of non-invasive clinical tests. A critical view on the current debate on serologic protein markers, e.g., lactate dehydrogenase, tyrosinase, and melanoma inhibiting activity, and some selected non-protein markers, e.g., 5-S-cysteinyl-dopa and circulating nucleic acids, will be offered and novel innovative approaches currently being explored will be discussed. Special emphasis is put on the S100 family of calcium binding proteins that is more and more emerging as a potentially important group of both molecular key players and biomarkers in the etiology, progression, manifestation, and therapy of neoplastic disorders, including malignant melanoma. Notably, S100B and, possibly, other S100 proteins like S100A4 are assumed to fulfill requirements which make them strong biomarker candidates in melanoma. Moreover, S100 proteins receive attention as possible targets of therapeutic intervention moving closer to clinical impact.

Evaluation of multiple serum markers in advanced melanoma

The aim of this retrospective study was to analyse in advanced melanoma the potential tumor markers S-100B, melanoma inhibiting activity protein (MIA) and YKL-40 compared to LDH. Serum levels of S-100B, MIA, LDH and YKL-40 were measured in 110 patients with advanced melanoma (36 in stage IIIB/C and 74 in stage IV), in 66 disease-free patients and in 65 healthy controls. Results show that S-100B, MIA and LDH levels were significantly higher in patients with advanced melanoma than in disease-free patients or healthy controls. The combination of S-100B plus MIA had the best diagnostic sensitivity, and the addition of LDH did not further increase this sensitivity. MIA was an independent prognostic factor of overall survival. Patients with both S-100B and MIA elevated had a significant shorter survival than those with both S-100B and MIA under the cut-off. YKL-40 levels did not differentiate patients with advanced melanoma from controls. We concluded that the combination of MIA plus S-100B showed a better prognostic value in advanced melanoma compared to LDH.

Serum markers of cutaneous melanoma

Malignant melanoma currently accounts for approximately 1%, of all cancer deaths. The incidence of cutaneous melanoma is rising worldwide. The treatment of early-stage melanoma consists primarily of surgical removal of the tumour. The overall 5-years survival rate for malignant melanoma is 81%. Recently, many efforts have been made to analyse the potential significance and the possible relationship of disease progression and circulating markers in malignant melanoma. Several serum biomarkers appear to hold significant potential both as prognostic indicators and as targets for future therapeutic agents. The application of these markers in clinical practice possibly holds the key to significant advances in melanoma. This review summarizes the principal characteristics of serum markers of melanoma. Serum lactate dehydrogenase (ldh), protein S-100 beta, melanoma-inhibiting activity (MIA) may correlate with melanoma progression. Tenascin-c, Hyaluronan, Laminin-1 and type VI Collagen are involved in melanoma development and extracellular matrix remodelling during melanoma progression.

Biomarkers in melanoma

Biomarkers are tumour- or host-related factors that correlate with tumour biological behaviour and patient prognosis. High-throughput analytical techniques—DNA and RNA microarrays—have identified numerous possible biomarkers, but their relevance to melanoma progression, clinical outcome and the selection of optimal treatment strategies still needs to be established. The review discusses a possible molecular basis for predictive tissue biomarkers such as melanoma thickness, ulceration and mitotic activity, and provides a list of promising new biomarkers identified from tissue microarrays that needs confirmation by independent, prospectively collected clinical data sets. In addition, common predictive serum biomarkers—lactate dehydrogenase, S100B and melanoma-inhibiting activity—as well as selected investigational serum biomarkers such as TA90IC and YKL-40 are also reviewed. A more accurate, therapeutically predictive classification of human melanomas and selection of patient populations that would profit from therapeutic interventions are among the major challenges expected to be addressed in the future.

Inhibitory effect of Listeria monocytogenes expressing melanoma-inhibiting activity gene on malignant melanoma.

Objective To investigate the inhibitory effects of L. monocytogenes expressing melanomainhibiting activity(MIA)gene on malignant melanoma.Methods The plasmid pERL3-hly-MIA was constructed and used to transform live L.monocytogenes by electroporation.Atier culture.the transformed L.monocytogenes,namely LM-hly-MIA,was harvested for the detection of MIA protein by Westem Blot.A total of 24 mice were divided into three groups,namely control group,LM group and LM-hly-MIA group,to be immunized with physiological saline,L.monocytogenes and LM-hly-MIA,respectively.One day after the immunization.mice were subcutaneously inoculated with 0.1 mL of B16 cells at a concentration of 1×107/mL.One week later.reimmunization was performed.The size and weight of tumors were observed and measured in these mice.Results Enzyme digestion and Western blot confirmed the Successful construction of plasmid pERL3-hly-MIA.The average weight of tumors in mice was 4.33±0.91 gram.3.36 ±0.41 gram and 1.89±0.52 gram,respectively in the control group,LM group and LM-hly-MIA group,respectively(P＜0.05).with the inhibition rates of tumor growth being 22.4%and 61.5%in LM group and LM-hly-MIA group.respectively.Conclusion The attenuated strain of L.monocytogenes expressing MIA gene could evidently inhibit melanoma growth. Key words: Melanoma; Listeria monocytogenes; Arrestin; Models,animal

A Comparison of 3 Tumor Markers (MIA, TA90IC, S100B) in Stage III Melanoma Patients

Purpose: There is no consensus regarding the optimal tumor markers for melanoma. We compared 3 tumor markers, TA90-immune complex (TA90IC), melanoma-inhibiting activity (MIA) protein, and S100B protein in Stage III melanoma patients undergoing adjuvant vaccine immunotherapy. Experimental design: The serum of 75 patients representing 3 prognostic cohorts was assayed for the tumor markers prior to initiating immunotherapy and at 6 follow-up time points. Upper limits of normal for TA90IC, MIA and S100B were set at OD 0.41, 8.5 ng/ml, and 2.5 μ g/l, respectively. Results: At least 1 marker became elevated prior to 41 (80 percent) of 51 recurrences. TA90IC was the earliest elevated marker in 29 (57 percent), MIA in 11 (22 percent), and S100B in 4 (8 percent). Multivariate regression analysis revealed that TA90IC was an independent predictor of survival when elevation occurred between 2 weeks and 3 months, whereas MIA was an independent predictor at 4–6 months. In the poor prognostic cohort, mean values for MIA and S100B increased progressively, whereas TA90IC exhibited a parabolic curve. Conclusion: In this patient population, TA90IC and MIA were complementary; elevation of the immune complex preceded elevation of the tumor antigen in patients who developed recurrence. Additional studies in populations not receiving vaccine will further clarify the clinical utility of these assays.

Molecular detection of MART-1, tyrosinase and MIA in peripheral blood, lymph nodes and metastatic sites of stage III/IV melanoma patients.

Melanoma lesions that develop in the same patient at different times or simultaneously at different locations may differ antigenically, because malignant melanoma is heterogeneous in terms of its biological, immunological and metastatic properties. The objective of this study was to characterize the molecular profiles of melanoma cells in peripheral blood, lymph nodes and metastatic tissues, employing the messenger RNA (mRNA) expression of tyrosinase, melanoma-inhibiting activity (MIA) and melanoma antigen recognized by T cells-1 (MART-1) as markers. Samples of cells propagated from metastatic sites were obtained from 17 stage III/IV melanoma patients and assayed by reverse transcriptase-polymerase chain reaction (RT-PCR), using specific primers for each marker. In eight patients, marker profiles were analysed in simultaneously obtained specimens of peripheral blood, lymph nodes and metastatic tissues originating from the same patient. Tyrosinase, MIA and MART-1 were expressed in 59%, 76% and 76% of the metastases, respectively. Simultaneously obtained specimens of peripheral blood, lymph nodes and metastatic tissues showed a high degree of homogeneity: 60%, 75% and 20% for tyrosinase, MIA and MART-1, respectively. Our findings suggest that the rather homogeneous expression pattern found in different tumour sites analysed in the same patient is of potential prognostic and therapeutic importance. Furthermore, melanoma lesions may be negative for the expression of antigens such as MART-1, and discrepancies in expression patterns between peripheral blood and metastatic tissues may occur, especially for this marker. Finally, our findings support the notion that molecular screening using an RT-PCR approach is appropriate in this kind of investigation.

Inhibition of immunosuppressive effects of melanoma-inhibiting activity (MIA) by antisense techniques.

Melanoma inhibitory activity (MIA) is an 11 kD protein secreted by malignant melanomas. Recent studies revealed an interaction of MIA with epitopes of extracellular matrix proteins including fibronectin. Structural homology of MIA with the binding sites of alpha4beta1 integrin results in complex interactions of MIA with molecules binding to alpha4beta1 integrin. As cells of the immune system express alpha4beta1 integrins (VLA-4), we investigated whether MIA may modulate the function of human leukocytes. 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. MIA inhibits PHA- or IL-2-induced human PBMC proliferation in a dose-dependent manner up to 63% ((3)H-Tdr incorporation) and 59% (cell count), respectively, when added to the cell culture prior to mitogen stimulation. In addition, both autologous (GL and HW) and allogeneic (HTZ-17, HTZ-243 and HTZ-374) antitumor LAK cytotoxicity was reduced by the addition of exogenous rhMIA (500 ng/ml, f.c.). Consequently, endogenous inhibition of MIA expression in human melanoma cells by MIA-specific phosphorothioate antisense oligonucleotides enhanced the autologous LAK-cell activity to the same level as observed in MIA-negative human HMB melanoma cells expressing an MIA-antisense construct. Our results indicate that MIA may contribute to immunosuppression frequently seen in malignant melanomas by inhibiting cellular antitumor immune reactions. Antagonization of MIA activity using antisense techniques may represent a novel therapeutic strategy for treatment of malignant melanomas.

Melanoma-inhibiting activity assay predicts survival in patients receiving a therapeutic cancer vaccine after complete resection of American Joint Committee on Cancer Stage III Melanoma.

More than half of melanoma patients rendered disease free by lymph node dissection will experience disease recurrence. We hypothesized that serum levels of melanoma-inhibiting activity (MIA) protein might be useful to stratify risk and identify subclinical recurrence in patients undergoing adjuvant immunotherapy. We examined MIA levels in the serum of stage III patients treated after surgery with a therapeutic cancer vaccine. Three cohorts of 25 patients were randomly selected from our melanoma database on the basis of time to death (group 1, <1 year; group 2, 1-5 years; group 3, >5 years.) Prospectively collected serum samples were assayed in a blinded fashion for MIA by enzyme-linked immunosorbent assay. MIA was increased at any time in 19 (76%) of 25, 4 (16%) of 25, and 1 (4%) of 25 patients in groups 1, 2, and 3, respectively. The median survival was 11 months for the 25 patients with increased MIA and >75 months for the 50 patients with normal MIA. MIA increased above normal a median of 1 month (mean, 75 days) before clinical recurrence. All patients with increased MIA after 2 months of treatment subsequently died of melanoma. One patient in whom initially increased levels decreased to normal within 2 months is disease free. Serum MIA levels provide important prognostic information early in the course of stage III melanoma and often detect melanoma recurrences before clinical evidence of disease.

Cloning and Characterization of the Expression Pattern of a Novel Splice Product MIA (Splice) of Malignant Melanoma-derived Growth-inhibiting Activity (MIAY CD-RAP)

Melanoma-inhibiting activity/cartilage-derived retinoic acid-sensitive protein, a 11 kDa protein, is mainly expressed in cartilage during embryogenesis, and is related to invasion, metastasis, and immunomodulation of melanoma and glioma cells in vivo and in vitro. Here, we describe an alternative splice product of this gene termed melanoma-inhibiting activity (splice), lacking exon 2 of the original protein. A predicted frameshift by alternate splicing results in a unique C-terminal portion of the protein. Consistent with this, a protein migrating at the predicted molecular weight of the splice form (3.5 kDa) was detected using an N-terminal specific antibody. This band was undetectable when using a C-terminal specific antibody. In addition, we describe the expression pattern of melanoma-inhibiting activity (splice) in different human tumors. Expression was shown in tissue samples of five of six primary melanomas, 11 of 12 primary sites of metastatic melanomas, 10 of 10 systemic metastases of melanomas, four of four central nervous system metastases of melanomas, six of eight primary melanoma cultures, and five of five melanoma cell lines. Only a faint signal was obtained in tissue samples of five of six naevi. Interestingly, seven of eight nonmelanocytic tissue samples and five of seven glioma cell lines showed weak expression of melanoma-inhibiting activity (splice). Approaching first functional aspects, reverse transcriptase-polymerase chain reaction showed weak expression of melanoma-inhibiting activity (splice) in relation to melanoma-inhibiting activity in nonmelanocytic and strong expression in melanocytic cells. Staining with a specific anti-serum raised against a synthetic peptide resembling the amino acid sequence of melanoma-inhibiting activity (splice) showed a more nuclear staining pattern in comparison with melanoma-inhibiting activity. Furthermore, incubation of melanoma and glioma cell cultures with transforming growth factor-beta2 showed inverse regulation of the mRNA of melanoma-inhibiting activity and melanoma-inhibiting activity (splice), both suggesting also a different function within the physiologic role of this unique family of proteins. Melanoma-inhibiting activity (splice) has no homology to any other known protein so far. Whereas the biologic function of melanoma-inhibiting activity (splice) is not clear yet, it might provide a relevant diagnostic and therapeutic tool for malignant melanomas.

Lösliche Serumfaktoren als prognostische Marker des Melanoms: sHLA, sFas und IL-8

A variety of serological markers have been identified in malignant melanoma, most of them associated with disease progression. Nevertheless, none of them is currently recommended for routine diagnostic use by international guidelines. S100-β, originally described as an acidic, calcium-binding protein derived from a bovine brain extract, has been demonstrated as an appropriate serum marker in metastatic melanoma patients with high serum levels indicating disease progression or recurrence. Moreover, S100-β has been proved as a useful serum parameter in the monitoring of metastatic melanoma patients during ongoing chemotherapy. Other serological marker proteins like e.g. melanoma inhibiting activity (MIA) have been evaluated in several studies, but could not be approved to exceed the predictive value of S100-β. A major disadvantage of S100-β is the poor predictive value of this marker in early-stage non-metastasized melanoma patients. After surgical removal of their primary tumors, these patients are enrolled into elaborated follow-up examination programs aiming at a detection of recurrence of the disease as early as possible. To estimate their risk of recurrence, these patients currently have to undergo invasive and costly procedures like e.g. sentinel lymph node dissection. Therefore, the identification of sensitive and reliable serological markers with strong predictive impact for the patients' prognosis would be of high beneficial value for this group of patients.

Serum levels of melanoma-inhibiting activity do not predict relapse in melanoma patients.

Melanoma-inhibiting activity (MIA) is a 107 amino-acid protein secreted from melanoma cells and frequently detectable at high concentration in the serum of patients with advanced melanoma. Early studies suggested that MIA may be a useful serum tumor-marker for detection of recurrent or progressive disease. We evaluated the sensitivity of serum MIA levels in predicting the risk of relapse in patients with American Joint Committee on Cancer (AJCC) Stage II, III, and IV melanoma. MIA was measured by ELISA in serum from 39 patients with AJCC Stage II, III and IV disease at a single time-point 1 month to 5 years after they were rendered free of disease. Twenty-three of the 39 patients recurred, with a median follow-up of 4.5 months. Only four of the 23 patients who recurred had shown elevated MIA values (17% sensitivity). Of the 16 patients who remain free of disease (median follow-up 3.5 years, range 11 months to 6.3 years), one patient had an elevated MIA. There was no significant difference in the proportion of patients with elevated serum MIA between the patients who recurred and those who remained free of disease. In this series, serum MIA was not a sensitive marker for relapse in patients who were clinically free of disease after treatment.

Seropositivity for MIA and S100 in patients with gastrointestinal carcinomas.

Serum levels of melanoma inhibiting activity (MIA) and S100, both markers in malignant melanoma, are increased only in few patients with non-melanocytic tumors. We examined a series of serum samples from patients with colorectal (CRC) (N=56), gastric (GC) (N=43), pancreatic (PC) (N=29), hepatocellular (HCC) (N=30), cholangiocellular and gallbladder carcinoma (CCC) (N=18). MIA and S100 were measured by commercially available assays. Positive serum levels for MIA and S100 were found in 16.1% and 5.4% of the patients with CRC, 11.6% and 9.3% with GC, 34.5% and 13.8% with PC, 0% and 30% with HCC and 16.7% with CCC, respectively. All patients with sera positive for either MIA or S100 suffered from advanced tumors and received palliative treatment. Elevated serum levels of MIA and S100 are frequent in patients with gastrointestinal cancer. Further investigation is warranted to define the role of MIA or S100 seropositivity in gastrointestinal cancer with regard to follow-up.

Melanoma-inhibiting activity (MIA) mRNA is not exclusively transcribed in melanoma cells: low levels of MIA mRNA are present in various cell types and in peripheral blood.

The detection of minimal amounts of melanoma cells by tyrosinase reverse transcription polymerase chain reaction (RT-PCR) is seriously hampered by false negative reports in blood of melanoma patients with disseminated melanoma. Therefore, additional assays which make use of multiple melanoma markers are needed. It has been shown that introduction of multiple markers increases the sensitivity of detection. Melanoma inhibitory activity (MIA) is one such melanoma-specific candidate gene. To test the specificity of MIA PCR, we performed 30 and 60 cycles of PCR with two different sets of MIA specific primers on 19 melanoma and 16 non-melanoma cell lines. MIA mRNA was detected in 16 out of 19 melanoma cell lines and in seven out of 16 non-melanoma cell lines after 30 cycles of PCR. However, MIA mRNA could be detected in all cell lines after 60 cycles of PCR. Also, in 14 out of 14 blood samples of melanoma patients, five out of six blood samples of non-melanoma patients and in seven out of seven blood samples of healthy volunteers, MIA mRNA was detected after 60 cycles of PCR, whereas no MIA PCR product could be detected in any of the blood samples after 30 cycles of PCR. We conclude that low levels of MIA transcripts are present in various normal and neoplastic cell types. Therefore, MIA is not a suitable marker gene to facilitate the detection of minimal amounts of melanoma cells in blood or in target organs of the metastatic process. © 1999 Cancer Research Campaign

S100-Beta, melanoma-inhibiting activity, and lactate dehydrogenase discriminate progressive from nonprogressive American Joint Committee on Cancer stage IV melanoma.

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. S100beta and MIA were supposed to be superior to conventional variables, such as lactate dehydrogenase (LDH) level. Seventy-one patients with stage IV malignant melanoma according to the criteria of the American Joint Committee on Cancer (AJCC) were included in the study. Results of restaging examinations were used as an independent reference standard for diagnosing progressive disease, and S100beta, MIA, LDH level, and erythrocyte sedimentation rate (ESR) were determined in venous blood just before restaging. Sensitivities and specificities of the parameters were calculated by logistic regression analysis. Discrimination ability was assessed by Somers' D(xy) rank correlation and the area under the receiver-operating characteristic curve (ROC-AUC). All tested serum parameters were significantly elevated in patients with progressive disease. The highest sensitivities according to the established thresholds were found for S100beta and MIA (91% and 88%, respectively). LDH had the highest specificity (92%). ESR was dropped from the analysis because of low specificity. In calculating Somers' D(xy) and ROC-AUC values, S100beta, MIA, and LDH showed high discrimination ability. By multiple logistic regression, LDH was identified to be the only statistically significant marker for progressive disease. S100beta and MIA did not provide additional significant information because of their high correlation with LDH with respect to clinical outcome. Elevated serum levels of S100beta, MIA, and LDH indicate current disease progression in AJCC stage IV melanoma. LDH was the most relevant overall parameter.

07 S-100B and melanoma inhibiting activity (MIA)

07 S-100B and melanoma inhibiting activity (MIA)

In situ expression patterns of melanoma-inhibiting activity (MIA) in melanomas and breast cancers.

Elevated levels of melanoma-inhibiting activity (MIA) were measured previously in the serum of patients with metastasized melanomas and in a subgroup of patients with advanced-stage breast cancers. This study aimed therefore to visualize in situ expression patterns of MIA protein and mRNA in melanomas and breast cancers by means of immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR), and in situ hybridization. Analysis of a panel of seven common melanocytic naevi, ten cutaneous melanomas, and 12 melanoma metastases detected high levels of both mRNA and protein in all melanomas and metastases, but only very low mRNA levels in three of seven naevi. 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. Expression was not detected in other skin tumours including basal cell cancers and squamous cell cancers, nor in normal melanocytes and keratinocytes. MIA expression in adenocarcinomas was further studied in a panel of 20 specimens obtained from 16 advanced-stage breast cancers and four metastases. Significant levels of mRNA were detected in 17 of the 20 specimens and low levels in the other three tumours. Immunostaining visualized specific protein expression in the tumour cells of all 20 cancer specimens. These investigations define for the first time in situ expression patterns of MIA in melanomas and breast cancers and suggest a much broader expression in malignant epithelial neoplasms than previously determined by serum studies.

Inhibition of melanoma cell proliferation and invasion by human and murine MIA (melanoma inhibiting activity)

Inhibition of melanoma cell proliferation and invasion by human and murine MIA (melanoma inhibiting activity)