Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression of matrix metalloproteinases (MMPs) is frequently altered during malignant transformation. We examined the profile of three recently cloned MMPs, MMP-21, MMP-26, and MMP-28, in melanomas in vivo and in culture. Immunohistochemistry for MMPs-21, -26, -28, and -13 in melanoma specimens (27 nonmetastatic, 26 with nodal micrometastases, and 10 in situ melanomas) from 63 patients was performed. MMP-21 was expressed in melanoma cells in 29/53 cases, being more frequent in melanoma samples without micrometastases. Six out of ten in situ melanomas were positive, while five nevus samples were negative. MMP-26 and -28 were not generally expressed in melanoma cells. MMP-13 was detected in melanoma cells in 36/53 samples. MMP-21 was not found in sentinel nodes with metastases, while MMP-13 was seen in all of them. MMP-21 messenger RNA was variably expressed in all five melanoma cell lines investigated using reverse transcriptase-polymerase chain reaction. Our results suggest that expression of MMP-21 may serve as a marker of malignant transformation of melanocytes and does not associate with the presence of micrometastases.
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PMID:MMP-21 is upregulated at early stages of melanoma progression but disappears with more aggressive phenotype. 1613 64

Pancreatic adenocarcinoma is known for early aggressive local invasion, high metastatic potential, and a low 5-year survival rate. Matrix metalloproteinases (MMPs) play important roles in tumor growth and invasion. Earlier studies on pancreatic cancer have found increased expression of certain MMPs to correlate with poorer prognosis, short survival time or presence of metastases. We studied the expression of MMP-21, -26, and tissue inhibitor of matrix metalloproteinases (TIMP)-4 in 50 tissue samples, including 25 adenocarcinomas, seven other malignant pancreatic tumors, and 18 control samples of non-neoplastic pancreatic tissue with immunohistochemistry. The regulation of MMP-21, -26, and TIMP-4 mRNAs by cytokines was studied with RT-PCR in pancreatic cancer cell lines PANC-1, BxPC-3, and AsPC-1. MMP-21, -26, and TIMP-4 were detected in cancer cells in 64, 40, and 60% of tumors, respectively. MMP-21 expressed in well-differentiated cancer cells and occasional fibroblasts, like TIMP-4, tended to diminish in intensity from grade I to grade III tumors. Patients with metastatic lymph nodes had increased expression of MMP-26 in actual tumor samples. All cultured cancer cell lines expressed MMP-21 basally at low levels, and presence of the protein was confirmed immunohistochemically in cultured cells. MMP-21 expression was induced by epidermal growth factor (EGF) in PANC-1 cells. MMP-26 was neither expressed basally nor induced by tumor necrosis factor alpha, transforming growth factor beta-1 (TGFbeta1), EGF, or interferon gamma. Basal TIMP-4 expression was lowest in the poorly differentiated cancer cell line PANC-1 compared to better-differentiated BxPC-3 and AsPC-1 cells. TIMP-4 expression was induced by TGFbeta1 in PANC-1 cells and by EGF in BxPC-3 cells. Our findings suggest that MMP-21 is not a marker of invasiveness, but rather of differentiation, in pancreatic cancer and it may be upregulated by EGF. The putative role of MMP-26 as a marker of metastases warrants further studies. Unlike other TIMPs, TIMP-4 was not upregulated in relation to aggressiveness of pancreatic cancer.
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PMID:Increased expression of matrix metalloproteinases-21 and -26 and TIMP-4 in pancreatic adenocarcinoma. 1787 96

The squamous cell cancers (SCC) of renal transplant recipients are more aggressive and metastasize earlier than those of the non-immunocompromised population. Matrix metalloproteinases (MMPs) have a central role in tumor initiation, invasion and metastasis. Our aim was to compare the expression of MMPs-10, -12 and -21 in SCCs from immunosuppressed (IS) and control patients and the contribution of MMPs-10 and -21 to SCC development in the FVB/N-Tg(KRT5-Nfkbia)3Rto mouse line. Immunohistochemical analysis of 25 matched pairs of SCCs, nine of Bowen's disease and timed back skin biopsies of mice with selective inhibition of Rel/NF-kappaB signalling were performed. Semiquantitatively assessed stromal MMP-10 expression was higher (P = 0.009) in the control group when compared with IS patients. Tumor cell-derived MMP-10, -12 and -21 expression did not differ between the groups but stromal fibroblasts of the control SCCs tended to express MMP-21 more abundantly. MMP-10 expression was observed already in Bowen's disease while MMP-21 was absent. MMP-10 and -21 were present in inflammatory or stromal cells in ageing mice while dysplastic keratinocytes and invasive cancer were negative. Our results suggest that MMP-10 may be important in the initial stages of SCC progression and induced in the stroma relating to the general host-response reaction to skin cancer. MMP-21 does not associate with invasion of SCC but may be involved in keratinocyte differentiation.
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PMID:MMP-10 (Stromelysin-2) and MMP-21 in human and murine squamous cell cancer. 1960 83

Merkel cell carcinoma (MCC) is an aggressive cutaneous tumor with poor outcome and increasing incidence. We examined by immunohistochemistry the expression of three novel matrix metalloproteinases (MMPs)-MMP-21, MMP-26, and MMP-28-in 44 primary MCC tumors and six lymph node metastases while MMP-10 served as a positive control. Their mRNA expression was also studied in the UISO MCC cell line basally and after various stimulations using quantitative real-time PCR. MMP-28 was observed in tumor cells of 15/44 samples especially in tumors <2 cm in diameter (p = 0.015) while 21/44 specimens showed MMP-28 in the tumor stroma. Expression of MMP-21 was demonstrated in tumor cells of 13/43 samples. MMP-26, instead, was positive in stromal cells (17/44) and its expression associated with tumors >or=2 cm in diameter (p = 0.006). Stromal expression of MMP-10 was the most frequent finding of the studied samples (31/44), but MMP-10 was detected also in tumor cells (17/44). Most of the metastatic lymph nodes expressed MMP-10 and MMP-26. MMP-10, MMP-21, and MMP-28 mRNAs were basally expressed by the UISO cells, and the corresponding proteins were detectable by immunostaining of cultured cells. IFN-alpha and TNF-alpha downregulated MMP-21 and MMP-28 expression. Our results suggest that novel MMPs may have a role in MCC pathogenesis: especially that MMP-26 expression in stroma is associated with larger tumors with poor prognosis. Expression of MMP-21 and MMP-28 seems to associate with the tumors of lesser malignant potential. We also confirm the previous finding on the role of MMP-10 in MCC pathogenesis.
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PMID:Expression of MMP-10, MMP-21, MMP-26, and MMP-28 in Merkel cell carcinoma. 1992 Dec 52

Matrix metalloproteinase (MMP)-21 and MMP-28, or epilysin, are overexpressed during the invasion and metastasis of solid tumors. The present study investigated MMP-21 and MMP-28 expression levels in human gastric cancer using tissue microarray (TMA) analysis, and determined their association with clinicopathological characteristics and patient prognosis. TMA blocks, including 436 cases of gastric cancer and 92 non-cancerous adjacent gastric tissues, were investigated using immunohistochemistry. Staining results were analyzed statistically in association with various clinicopathological characteristics and overall survival. The MMP-21 and MMP-28 positive detection rate was 31.9% (139/436) and 34.4% (150/436), respectively, in the gastric carcinoma tissue specimens. MMP-21 and MMP-28 expression levels were negative in the 92 normal gastric tissue samples. In patients with gastric cancer, positive expression of MMP-21 and MMP-28 was correlated with tumor diameter, depth of invasion, vessel invasion, lymph node and distant metastases and tumor-node-metastasis stage. The overall survival rate was significantly lower in MMP-21 and MMP-28-positive compared with negative patients. Cox multivariate analysis revealed that MMP-21 and MMP-28 levels were independent predictors of survival in patients with gastric cancer. These findings emphasize the importance of MMP-21 and MMP-28, which may serve as novel and independent prognostic markers for the invasion and metastasis of human gastric cancer.
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PMID:Overexpression of MMP21 and MMP28 is associated with gastric cancer progression and poor prognosis. 2973 3