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

The local growth of tumors and their ability to metastasize are crucially dependent on their interactions with the surrounding extracellular matrix. Tenascin-C (TNC) is an extracellular matrix protein which is highly expressed during development, tissue repair and cancer. Despite the high levels of TNC in the stroma of primary and metastatic tumors, the function of TNC is not known. In the present study we have crossed TNC-null mice with a mouse strain where both female and male mice spontaneously develop mammary tumors followed by metastatic disease in the lungs. We report that the absence of TNC had no effect on the temporal occurrence of mammary tumors and their metastatic dissemination in lungs. Furthermore, the number and size of tumors, the number and size of metastatic foci in the lungs, the proliferation rate and apoptosis of tumor cells and tumor angiogenesis were not altered in the absence of TNC. Histological examination revealed that the tumor organisation, however, was modulated by TNC. In the presence of TNC both primary as well as metastatic tumors were organised in large tumor cell nests surrounded by thick layers of extracellular matrix proteins. In the absence of TNC these tumor cell nests were smaller but still separated from each other by extracellular matrix proteins. In addition, the TNC-null stromal compartment contained significantly more monocytes/macrophages than tumor stroma from TNC wild-type mice. Using in vitro coculture experiments we show that TNC-null tumor cells were still able to activate the TNC gene in fibroblasts which express low basal levels of TNC. Altogether these data indicate that TNC has a very limited role during the spontaneous development and growth of mamary tumors and their metastasis to the lungs.
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PMID:Tenascin-C modulates tumor stroma and monocyte/macrophage recruitment but not tumor growth or metastasis in a mouse strain with spontaneous mammary cancer. 1034 Dec 5

Tenascin-C (TN-C) is one of extracellular matrix glycoproteins. We have immunohistochemically examined the TN-C expression of 33 primary osteosarcoma paraffin-embedded samples. The TN-C expression of the patient group with metastases was higher than that of the group without metastases at significant difference, and the survival curves show a tendency for poor outcome in the high grade staining group. Moreover, the supplemental TN-C had an effect of easier migration of a human osteosarcoma cell line (HOS) in vitro. The results may suggest that TN-C help osteosarcoma cells to migrate and to metastasize.
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PMID:Clinical significance of tenascin-C expression in osteosarcoma: tenascin-C promotes distant metastases of osteosarcoma. 1076 53

Oesophageal adenocarcinoma is believed to arise from metaplastic mucosa in the distal oesophagus, a condition also known as Barrett's oesophagus (BE). BE develops as a result of injury caused by refluxing gastric and duodenal contents and is associated with increased risk of malignant transformation. Matrix metalloproteinases (MMPs) have been implicated in all aspects of tumour progression; tumour growth, basement membrane degradation, invasion and metastatic spread. Using in situ hybridization, we investigated the expression patterns of collagenases-1 and -3, stromelysin-2, matrilysin, metalloelastase and TIMPs-1 and -3 in BE, adenocarcinoma and lymph-node metastases. Matrilysin was expressed abundantly in 12/15 tumours and in 4/6 lymph-node metastases and its expression correlated with the histological aggressiveness of tumour. Matrilysin and metalloelastase were upregulated already in BE. Stromelysin-2 and collagenase-3 expression was detected only in a few tumours. Collagenase-1 was expressed by cancer and stromal cells in 9/15 tumours. Tumour-infiltrating macrophages expressed metalloelastase in 13/15 cancers. TIMPs-1 and -3 were expressed in 12/15 and 11/15 tumours, respectively. Laminin-5 and tenascin were abundantly expressed at the invasive front of poorly differentiated tumours, but not in BE. Our results indicate that matrilysin is the principal MMP expressed by tumour cells in oesophageal adenocarcinoma, and further studies are needed to investigate whether matrilysin or tenascin-C could be used as a predictive marker for progression of BE to cancer.
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PMID:Upregulation and differential expression of matrilysin (MMP-7) and metalloelastase (MMP-12) and their inhibitors TIMP-1 and TIMP-3 in Barrett's oesophageal adenocarcinoma. 1148 70

Expression of tenascin-C (Tn-C) has been shown to correlate with invasion and metastasis in Merkel cell carcinoma (MCC). Cytokeratin-20 (CK-20) is used in differential diagnostics of the primary tumour. The aim of this study was to demonstrate the expression of Tn-C in MCC lymph node metastases. Immunohistochemical staining was performed for five metastatic lymph nodes using a monoclonal antibody against Tn-C and CK-20. All five metastatic lymph nodes expressed Tn-C. The expression concentrated around the vascular structures, invasion borders and fibrotic septae. One of the metastatic lymph nodes was strongly positive for CK-20 while the others showed a focal or negative pattern. The normal lymphoid tissue was negative for Tn-C. Tn-C detected metastatic MCC tissue within the lymph nodes undisputedly. There was a clear distinction between the metastatic and normal lymphatic tissue. Furthermore, invasion to the surrounding tissue was easily demonstrated. Contrary to previous studies, CK-20 expression seemed to fluctuate.
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PMID:Tenascin-C expression in Merkel cell carcinoma lymph node metastasis. 1649 59

Malignant melanomas are characterized by their high propensity to invade and metastasize, but the molecular mechanisms of these traits have remained elusive. Our DNA microarray analyses of benign nevi and melanoma tissue specimens revealed that the genes encoding extracellular matrix proteins tenascin-C (TN-C), fibronectin (FN), and procollagen-I (PCOL-I) are highly upregulated in invasive and metastatic melanomas. The expression and distribution of these proteins were further studied by immunohistochemistry in benign nevi, radially and vertically growing melanomas, sentinel node micrometastases, and macrometastases. TN-C was increased in all invasive tumours and metastases, especially at invasion fronts, but not in benign nevi or non-invasive melanomas. Significantly, the intensity of TN-C staining correlated with metastasis to sentinel lymph nodes, better than tumour thickness (Breslow). Moreover, TN-C, FN, and PCOL-I appeared to co-localize in the tumours and form tubular meshworks and channels ensheathing the melanoma cells. Our data suggest that melanoma invasion is associated with the formation of special channel-like structures, providing a new concept, structured tumour cell spreading. Altogether, these data provide potential new prognostic markers and therapeutic targets/strategies for preventing melanoma dissemination.
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PMID:Switch to an invasive growth phase in melanoma is associated with tenascin-C, fibronectin, and procollagen-I forming specific channel structures for invasion. 1692 94

The formation of a fibrotic capsule around liver metastases may functionally act as a barrier to local invasion. However, the prognostic significance of exstracellular matrix (ECM) and of some integrins' deposition around liver metastases remains unclear. An immunohistochemical investigation was carried out on 55 patients with synchronous liver metastases from colorectal and gastric cancers. Encapsulated metastases were detected in 60% of the cases. The 'non-capsular' cases showed clear immunostaining for tenascin-C, fibronectin, collagen IV, laminin, alphaSMA and integrins. On opposite, most of the cases with 'capsule' were negative for the studied ECM proteins and the two integrins. The patients with 'capsular' pattern had significantly longer median survival after the surgery compared to those with non-encapsulated metastases. The presence of tenascin, fibronectin, fibronectin receptor and laminin, as well as the strong immune signal for alphaSMA and collagen type IV in the sinusoids attached to the liver metastases was associated with a worse prognosis. The cells, forming ECM in the sinusoids attached to metastases in the 'non-capsular' pattern were alphaSMA-positive myofibroblasts. It was shown ultrastructurally that they were HSCs. The results indicate that fibrotic capsule formation is associated with longer survival after surgery. The appearance of tenascin-C and of its receptor at the periphery of liver metastases could be used as a sign of invasiveness.
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PMID:Significance of tenascin-C, fibronectin, laminin, collagen IV, alpha5beta1 and alpha9beta1 integrins and fibrotic capsule formation around liver metastases originating from cancers of the digestive tract. 1701 31

Medullary thyroid carcinomas are aggressive neoplasias that metastasize very early to loco-regional lymph nodes, and tumors with a desmoplastic stromal reaction have a higher incidence of lymph node metastasis. In order to characterize the desmoplastic response in thyroid cancers, we evaluated the expression pattern of three molecular markers of activated fibroblasts/myofibroblasts, namely, fibroblast activation protein alpha (FAPalpha), tenascin-C (Tn-C), and alpha-smooth muscle actin (alpha-SMA), as well as the endothelial markers endoglyx-1, CD34 and CD31 in a series of 28 metastatic and non-metastatic medullary thyroid cancers. Immunohistochemical studies demonstrated that the three fibroblast activation markers (FAPalpha, Tn-C, alpha-SMA) are consistently expressed in the peritumoral and intratumoral stromal compartment of medullary thyroid carcinomas and expression of FAPalpha and Tn-C correlated with the degree of desmoplasia determined histologically (p=0.001 for FAPalpha and p<0.001 for Tn-C). Moreover, the extent of desmoplasia as well as the expression of FAPalpha and Tn-C correlated with the presence of lymph node (LN) metastases (p=0.002, p=0.005 and p=0.002, respectively). No correlation was found between the microvessel density (neoangiogenesis) in the tumor stroma, assessed with the endoglyx-1, CD34 and CD31 markers, and the degree of desmoplasia or incidence of LN metastases. Using a bioinformatics-based search of the BioExpresstrade mark database we found in a series of 48 thyroid cancers a significant correlation between FAPalpha RNA expression and incidence of LN metastases also in papillary cancers. These findings suggest that the link between specific molecular markers of tumor stromal reaction and locoregional metastasis extends from medullary to other thyroid cancer types.
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PMID:Molecular characterization of the desmoplastic tumor stroma in medullary thyroid carcinoma. 1754 5

Metastasis is the primary cause of death in patients with breast cancer. Overexpression of c-myc in humans correlates with metastases, but transgenic mice only show low rates of micrometastases. We have generated transgenic mice that overexpress both c-myc and vascular endothelial growth factor (VEGF) (Myc/VEGF) in the mammary gland, which develop high rates of pulmonary macrometastases. Gene expression profiling revealed a set of deregulated genes in Myc/VEGF tumors compared to Myc tumors associated with the increased metastatic phenotype. Cross-comparisons between this set of genes with a human breast cancer lung metastasis gene signature identified five common targets: tenascin-C(TNC), matrix metalloprotease-2, collagen-6-A1, mannosidase-alpha-1A and HLA-DPA1. Signaling blockade or knockdown of TNC in MDA-MB-435 cells resulted in a significant impairment of cell migration and anchorage-independent cell proliferation. Mice injected with clonal MDA-MB-435 cells with reduced expression of TNC demonstrated a significant decrease (P<0.05) in (1) primary tumor growth; (2) tumor relapse after surgical removal of the primary tumor and (3) incidence of lung metastasis. Our results demonstrate that VEGF induces complex alterations in tissue architecture and gene expression. The TNC signaling pathway plays an important role in mammary tumor growth and metastases, suggesting that TNC may be a relevant target for therapy against metastatic breast cancer.
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PMID:Identification of VEGF-regulated genes associated with increased lung metastatic potential: functional involvement of tenascin-C in tumor growth and lung metastasis. 1850 37

Angiogenesis, the formation of new blood vessels, is a multi-step process regulated by pro- and anti-angiogenic factors. In order to grow and metastasize, tumors need a constant supply of oxygen and nutrients. For their growth beyond the size of 1-2 mm tumors are dependent on angiogenesis. Recently, various new anti-cancer agents (e.g. bevacizumab, sorafenib and sunitinib) have become available that specifically inhibit angiogenesis in tumors. To evaluate the effects of these new anti-angiogenic agents it would be of interest to scintigraphically image the process of angiogenesis in tumors. Several markers have been described that are preferentially expressed on newly formed blood vessels in tumors (alpha(v)beta(3) integrin, vascular endothelial growth factor and its receptor, prostate-specific membrane antigen) and in the extracellular matrix surrounding newly formed blood vessels (extra-domain B of fibronectin, Tenascin-C, matrix metalloproteinases, Robo-4). Several ligands targeting these markers have been tested as a radiotracer for imaging angiogenesis in tumors. The potential of some of these tracers such as radiolabeled cyclic RGD peptides and radiolabeled anti-PSMA antibodies has already been tested cancer patients, while for markers such as Robo-4 the ligand has not yet been identified. Here the preclinical and clinical studies with these new tracers to image angiogenesis in tumors are reviewed.
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PMID:New targeted probes for radioimaging of angiogenesis. 1931 27

Angiogenesis is a multistep process regulated by pro- and antiangiogenic factors. In order to grow and metastasize, tumors need a constant supply of oxygen and nutrients. For growth beyond 1-2 mm in size, tumors are dependent on angiogenesis. Inhibition of angiogenesis is a new cancer treatment strategy that is now widely investigated clinically. Researchers have begun to search for objective measures that indicate pharmacologic responses to antiangiogenic drugs. Therefore, there is a great interest in techniques to visualize angiogenesis in growing tumors noninvasively. Several markers have been described that are preferentially expressed on newly formed blood vessels in tumors (alpha(v)beta(3) integrin, vascular endothelial growth factor, and its receptor, prostate-specific membrane antigen) and in the extracellular matrix surrounding newly formed blood vessels (extra domain B of fibronectin, Tenascin-C, matrix metalloproteinases, and Robo-4). Several ligands targeting these markers have been tested as a radiotracer for imaging angiogenesis in tumors. The potential of some of these tracers, such as radiolabeled cyclic RGD peptides and radiolabeled anti-PSMA antibodies, has already been tested in cancer patients, while for markers such as Robo-4, the ligand has not yet been identified. In this review, an overview on the currently used nuclear imaging probes for noninvasive visualization of tumor angiogenesis is given.
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PMID:Radionuclide imaging of tumor angiogenesis. 2002 43


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