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)

Pigment epithelium-derived factor, a potent angiogenesis inhibitor in the eye, is also expressed in the prostate. Prostate size and angiogenesis is increased in pigment epithelium-derived factor knockout mice, and pigment epithelium-derived factor is down-regulated in some prostate cancers. To investigate whether pigment epithelium-derived factor expression correlates with tumor progression, we examined 5 Dunning rat prostate sublines with different growth rates, differentiation, androgen dependence, vascular density, and metastatic ability and 26 human prostate cancers of Gleason score 8-10 obtained from patients at transurethral resection selected to represent two groups, with and without metastases at diagnosis. By Western blot, real-time quantitative reverse transcription-PCR, and immunostaining, pigment epithelium-derived factor was detected in highly differentiated, nonmetastatic, androgen-sensitive Dunning tumors and in the anaplastic, androgen insensitive but nonmetastatic Dunning tumors. In contrast, the metastatic Dunning tumor sublines showed very low pigment epithelium-derived factor expression levels. In human cancer tissues, by immunohistochemistry and real-time quantitative reverse transcription-PCR, patients without metastases at diagnosis had higher tumor pigment epithelium-derived factor levels than tumors from patients with metastases at diagnosis. In both the rat model and in the human tumors, the proliferation index and vascular count, as determined by Ki-67 staining and endoglin and/or factor VIII-related antigen staining, inversely correlated with pigment epithelium-derived factor mRNA levels. These observations indicate that loss of pigment epithelium-derived factor expression could be associated with the progression toward a metastatic phenotype in prostate cancer.
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PMID:Decreased pigment epithelium-derived factor is associated with metastatic phenotype in human and rat prostate tumors. 1531 5

Endoglin (CD105), a member of transforming growth factor beta1 receptor complex, has been shown to be a more useful marker to identify tumor angiogenesis than panendothelial markers such as CD31. We investigated endoglin and vascular endothelial growth factor (VEGF) expression as possible prognostic markers in esophageal adenocarcinoma. Surgical specimens from 75 patients with esophageal adenocarcinoma treated with esophagectomy were immunostained for endoglin, CD31, and VEGF. We also included 10 cases of Barrett's esophagus with high-grade dysplasia and 10 cases with Barrett's esophagus low-grade dysplasia. Positively stained microvessels (MVs) were counted in hot spots at magnification of x400. Results were expressed as the highest number of MV identified. For VEGF, intensity of staining was scored on 3-tiered scale. Endoglin demonstrated significantly more vessels than the CD31 (mean, 28.9 +/- 13.2 versus 19.0 +/- 9.4, P < .001). Both endoglin and CD31 MV counts showed significant correlation with stage of the disease (r = 0.59, P < .001; r = 0.52, P < .001, respectively) and patient survival (log rank P < .01). Only endoglin MV count was significantly correlated with the presence of angiolymphatic invasion (r = 0.34, P < .05) and lymph node (LN) metastases (r = 0.48, P < .001). Univariate analysis showed that endoglin MV count is an independent prognostic factor. Endoglin showed a significant increase in MV count in Barrett's esophagus with high-grade dysplasia when compared with Barrett's esophagus low-grade dysplasia (P < .01), whereas CD31 did not show any significant difference. VEGF was expressed in 48 (64%) of 75 cases of adenocarcinoma and was significantly correlated with angiolymphatic invasion, LN metastases, and survival. In conclusion, endoglin is a specific and sensitive marker for tumor angiogenesis. Endoglin staining also showed prognostic significance with positive correlation with the presence of angiolymphatic invasion, LN metastases, tumor stage, and survival.
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PMID:Endoglin (CD105) and vascular endothelial growth factor as prognostic markers in esophageal adenocarcinoma. 1615 57

Endoglin (CD105), a co-receptor in the TGF-beta receptor complex, is over-expressed on proliferating endothelial cells in the breast tumor neovasculature and thus offers an attractive target for anti-angiogenic therapy. Here we report the anti-angiogenic/anti-tumor effects achieved in a prophylactic setting with an oral DNA vaccine encoding murine endoglin, carried by double attenuated Salmonella typhimurium (dam-, AroA-) to a secondary lymphoid organ, i.e., Peyer's patches . We demonstrate that an endoglin vaccine elicited activation of antigen-presenting dendritic cells, coupled with immune responses mediated by CD8+ T cells against endoglin-positive target cells. Moreover, we observed suppression of angiogenesis only in mice administered with the endoglin vaccine as compared to controls. These data suggest that a CD8+ T cell-mediated immune response induced by this vaccine effectively suppressed dissemination of pulmonary metastases of D2F2 breast carcinoma cells presumably by eliminating proliferating endothelial cells in the tumor vasculature. It is anticipated that vaccine strategies such as this may contribute to future therapies for breast cancer.
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PMID:Endoglin (CD105) is a target for an oral DNA vaccine against breast cancer. 1656 28

The ability of neoplastic cells to dissemination from a primary tumor to lymphatic nodes and to adjacent and distant tissues and organs is an inseparable feature of malignant tumors and the main cause of failure in their treatment. Metastasis formation is a multistage process which includes proteolysis, the motility and migration of cells, proliferation, and neoangiogenesis. In the first step, the cells released from the primary tumor have to penetrate to the blood or lymphatic vessels (intravasation), the road which dissemination follows. Circulating cells can then migrate through the walls of vessels to surrounding tissues (extravasation) where they settle, proliferate, and induce angiogenesis, creating metastases. Indispensable in the process of intra- and extravasation is the activation of proteolytic enzymes capable of degrading the extracellular matrix (ECM) surrounding the endothelium or creating the basement membrane of epithelial tissue in different organs. In this stage, the activation of proteolytic enzymes, such as proteinases of the plasmin system, serine proteinases, and matrix metalloproteinases (MMPs), is necessary. Simultaneously, changes occur in the expression of many superficial glycoproteins and factors responsible for cell adhesion (integrins) and intercellular communication (cadherins). Neoangiogenesis is connected with the expression of many markers of this process, among them vascular endothelial growth factor (VEGF), endoglin (CD105), a transmembranous glycoprotein which is a component of the receptor for transforming growth factor beta (TGFbeta), as well as neuropilin (NRP), the co-receptor for VEGF. Conventionally, the prognosis of neoplastic disease and its treatment are based mainly on exact clinical and histopathological staging. This prognosis could, however, be improved by measuring the molecular and cellular markers which play key roles in tumor progression. Understanding the cellular processes responsible for tumor dissemination can be useful not only in the diagnosis and prognosis of treatment results, but also in developing targeted drugs, selectively directed towards those factors responsible for tumor invasiveness, as well as in creating new therapeutic strategies permitting the use of such drugs. In the present review the authors concentrate mainly on one tumor type, colorectal carcinoma, in which distant metastases, predominantly to the liver, are the main cause of failure, in spite of surgical curing of the primary tumor.
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PMID:[Mechanisms of metastasis and molecular markers of malignant tumor progression. I. Colorectal cancer]. 1701 65

We studied endoglin and vascular endothelial growth factor (VEGF) expression as prognostic markers in prostatic adenocarcinoma in 50 radical prostatectomy specimens. Cases were further categorized by Gleason score as follows: 8 to 10, 9 cases; 7(4 + 3), 9 cases; 7 (3 + 4), 14 cases; 6, 13 cases; and 4 or 5, 5 cases. All cases were immunostained for endoglin, CD31, and VEGF. Positively stained microvessels were counted in densely vascular foci in a x 400 field. VEGF staining intensity was scored on a 2-tiered scale. Results were correlated with survival and other parameters. Endoglin demonstrated significantly more microvessels than did CD31 (mean +/- SD, 37 +/- 15 vs 22 +/- 17; P < .001). VEGF expression was low in 21 cases (42%) and high in 29 (58%). Endoglin correlated positively with Gleason score, lymph node metastases, tumor stage, and preoperative prostate-specific antigen level (P < .05) but not with CD31. VEGF correlated significantly with angiolymphatic invasion and Gleason score (P < .05). A high endoglin microvessel count and VEGF expression correlated with shorter survival. Endoglin is a more specific and sensitive marker for tumor angiogenesis than CD31 and may serve as a prognostic marker for prostatic adenocarcinoma.
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PMID:Endoglin (CD105) and vascular endothelial growth factor as prognostic markers in prostatic adenocarcinoma. 1736 32

Primary hepatic epithelioid hemangioendothelioma (HEH) is a rare, low-grade malignant neoplasm of endothelial origin, with an unpredictable clinical course and prognosis. No standard therapeutic strategies are still available for HEH, due to the infrequency of the disease and to its variable natural history that limit the identification of the most effective treatment. In the absence of metastatic disease, surgical resection or liver transplantation represent the treatment of choice for HEH, while several antineoplastic agents have been proposed in the presence of metastatic nonresectable disesase. Herein, we describe the biological characterization and the clinical course of a primary HEH progressively responsive to treatment with intermediate doses of interferon-alpha (IFN)-alpha2a. Furthermore, based on the newly-identified expression of endoglin (CD105) on HEH, we discuss the clinical potential of novel anti-angiogenetic approaches to the disease.
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PMID:Primary hepatic epithelioid hemangioendothelioma progressively responsive to interferon-alpha: is there room for novel anti-angiogenetic treatments? 1755 Jan 44

Brain metastases are linked to poor prognosis. After carcinomas of the lung and breast, malignant melanomas (MM) are the next type of neoplasm with the higher metastatic dissemination involving the central nervous system and that has the worst prognosis after metastasis has been diagnosed. Angiogenesis has been linked to tumor growth and metastasis. Among the immunomarkers of angiogenesis, endoglin (CD105) is the most specific antibody, since it is a marker for tumor endothelium, and expression of CD105 has been observed to be associated with prognosis in several types of tumor, which is not always observed in melanomas. This study investigated angiogenesis in brain metastasis secondary to malignant melanomas and compared these with brain metastasis secondary to carcinomas of the lung and breast, through expression of CD105 (endoglin). The study investigated 93 cases of brain metastasis secondary to MM (33) and carcinomas of the lung (31) and breast (29), assessing endoglin immunoexpression, number of microvessels and diameter of tumor vessels. Tumor microvessels were counted using a modified version of the Chalkley technique. The observed difference between MM and breast carcinoma was statistically significant (P = 0.026). The difference between MM and lung carcinoma was not significant (P = 0.218). Vascular diameter observation revealed no statistical difference between the vascular size of neoplastic vessels in MM and in breast and lung carcinomas. Of the tumors investigated here, malignant melanomas were shown to have the lowest number of microvessels and had intermediate tumor vessel diameter as compared to carcinomas of the lungs and breast. Such results were not expected to be found in neoplasms such as melanomas that, besides presenting high dissemination capacity, have a high index of hemorrhage secondary to brain metastasis.
Clin Exp Metastasis 2007
PMID:Immunoexpression of endoglin in brain metastasis secondary to malignant melanoma: evaluation of angiogenesis and comparison with brain metastasis secondary to breast and lung carcinomas. 1756 91

A dynamic interplay between prostate cancer cells and reactive bone stroma modulates growth of metastases within bone. We used microarray analysis to screen for changes in gene expression in bone marrow stromal cells cocultured with prostate cancer cells and found reduced expression of endoglin, a transmembrane glycoprotein that functions as an auxiliary coreceptor for members of the transforming growth factor beta (TGF-beta) family of cytokines. The downstream TGF-beta/bone morphogenetic protein signaling pathway including Smad1 and Smad2/3 also was attenuated, as was Smad-dependent gene transcription. Smad1/5/8-dependent inhibitor of DNA binding 1 expression and Smad2/3-dependent plasminogen activator inhibitor I expression both were decreased and were accompanied by decreased cell proliferation. Small interfering RNA-mediated knockdown of endoglin in HS-5 cells verified that the effects on signaling were a direct result of the attenuation of endoglin. These data illustrate that endoglin acts as a positive regulator of both activin receptor-like kinase 1-induced Smad1/5/8 activation and activin receptor-like kinase 5-induced Smad2/3 activation in bone marrow stromal cells. In addition, the data illustrate that one early event of metastasis upon the arrival of prostate cancer cells into the bone stroma is attenuated endoglin expression in the stromal cells, which subsequently alters Smad signaling and cell proliferation. We hypothesize that coculture of bone marrow stromal cells with prostate cancer cells alters TGF-beta signaling in the stromal cells, ultimately facilitating growth of the cancer cells in the bone compartment. Collectively, these studies suggest that prostate cancer cells modulate TGF-beta responsiveness of bone marrow stroma as one means of facilitating their own growth in bone.
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PMID:Coculture with prostate cancer cells alters endoglin expression and attenuates transforming growth factor-beta signaling in reactive bone marrow stromal cells. 1757 18

Endoglin (CD105) is an accessory protein of the transforming growth factor-beta receptor system expressed on vascular endothelial cells. Mutation of the endoglin gene is associated with hereditary hemorrhagic telangiectasias, or Osler-Weber-Rendu syndrome, and has been studied extensively in the context of this disease. The expression of endoglin is elevated on the endothelial cells of healing wounds, developing embryos, inflammatory tissues, and solid tumors. Endoglin is a marker of activated endothelium, and its vascular expression is limited to proliferating cells. Recent studies identified endoglin expression in several solid tumor types, with the level of expression correlating with various clinicopathologic factors including decreased survival and presence of metastases. Attempts to target endoglin and the cells that express this protein in tumor-bearing mice have yielded promising results.
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PMID:Endoglin (CD105): a marker of tumor vasculature and potential target for therapy. 1838 30

Cutaneous melanoma preferentially metastasizes via the lymphatic route. However, the mechanisms of lymphatic invasion and metastasis to regional lymph nodes are poorly understood. Nitric oxide is a free radical molecule synthesized from L-arginine by nitric oxide synthases that plays a critical role in various physiological and pathological processes, including tumor growth and angiogenesis. We have tested whether inducible nitric oxide synthase expression correlates with lymphatic vessel density identified with D2-40 antibody and/or blood microvessel density identified with CD105/endoglin in a series of melanocytic nevi (n=28) and cutaneous melanomas (n=38), representative of various pT. Inducible nitric oxide synthase expression was significantly lower in melanocytic nevi in comparison with primary and metastatic melanomas (P<0.001). Mean microvessel density was significantly higher in primary and metastatic melanomas in comparison with melanocytic nevi (P<0.001 for intratumoral and P=0.001 for peritumoral vessels). Vertical growth phase melanomas showed a higher intratumoral microvessel density in comparison with radial growth phase melanomas (P=0.02). The number of peritumoral lymphatics was significantly lower in nevi as compared with primary and metastatic melanomas (P=0.01). No correlation between microvessel or lymphatic vessel and clinical outcome was found in melanomas. A significant direct correlation was observed between inducible nitric oxide synthase immunostaining in melanocytic tumor cells and the density of lymphatic vessels (peritumoral: P=0.001; intratumoral: P=0.08), and the density of peritumoral blood microvessel (P=0.02). Our findings support the hypothesis that inducible nitric oxide synthase is implicated not only in blood, but also in lymphatic vascular neoformation in melanoma. Mechanistic studies are needed to address the possibility that inducible nitric oxide synthase controls lymphangiogenesis, dissemination and lymphatic borne metastases.
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PMID:Inducible nitric oxide synthase expression in melanoma: implications in lymphangiogenesis. 1866 Jul 96


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