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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Blood vessels and lymphatic vessels form extensive networks that are essential for the transport of fluids, gases, macromolecules and cells within the large and complex bodies of vertebrates. Both of these vascular structures are lined with endothelial cells that integrate functionally into different organs, acquire tissue-specific specialization and retain plasticity; thereby, they permit growth during tissue repair or in disease settings. The angiogenic growth of blood vessels and lymphatic vessels coordinates several biological processes such as cell proliferation, guided migration, differentiation and cell-cell communication.
Nat Rev Mol Cell Biol 2007 Jun
PMID:Molecular regulation of angiogenesis and lymphangiogenesis. 1752 91

Lymphatic-vasculature function critically depends on extracellular matrix (ECM) and on its connections with lymphatic endothelial cells (LECs). However, the composition and the architecture of ECM have not been fully taken into consideration in studying the biology and the pathology of the lymphatic system. EMILIN1, an elastic microfibril-associated protein, is highly expressed by LECs in vitro and colocalizes with lymphatic vessels in several mouse tissues. A comparative study between WT and Emilin1-/- mice highlighted the fact that Emilin1 deficiency in both CD1 and C57BL/6 backgrounds results in hyperplasia, enlargement, and frequently an irregular pattern of superficial and visceral lymphatic vessels and in a significant reduction of anchoring filaments. Emilin1-deficient mice also develop larger lymphangiomas than WT mice. Lymphatic vascular morphological alterations are accompanied by functional defects, such as mild lymphedema, a highly significant drop in lymph drainage, and enhanced lymph leakage. Our findings demonstrate that EMILIN1 is involved in the regulation of the growth and in the maintenance of the integrity of lymphatic vessels, a fundamental requirement for efficient function. The phenotype displayed by Emilin1(-/-) mice is the first abnormal lymphatic phenotype associated with the deficiency of an ECM protein and identifies EMILIN1 as a novel local regulator of lymphangiogenesis.
Mol Cell Biol 2008 Jun
PMID:Emilin1 deficiency causes structural and functional defects of lymphatic vasculature. 1841 5

These experiments were conducted to investigate whether the antimetastatic effects of HSVtk/GCV therapy involve T-cell-mediated immune responses. In the first experiment, immunocompetent syngeneic mice were inoculated with metastatic mammary cancers, then given a direct intratumoral injection of a plasmid vector containing a suicide gene (pHSVtk) or control vector once a week for 8 weeks. Gene electrotransfer treatment was applied to the tumors, and mice were administered ganciclovir (GCV) using a mini-osmotic pump. At the end of the experiment, tumor volume was significantly lower in the pHSVtk/GCV group. Macrophage accumulations were frequently observed in the peripheries of the necrotic regions in pHSVtk-transfected mice. Levels of CD4 and CD8 proteins in tumors were higher in the pHSVtk/GCV group than in the control group. Interleukin (IL)-12 mRNA levels tended to be higher in tumors in the pHSVtk/GCV group, but there were large variations. Tumor microvessel density was significantly lower in the pHSVtk/GCV group. The numbers of dilated lymphatic vessels containing intraluminal tumor cells tended to be higher in the pHSVtk/GCV group. However, vascular endothelial growth factor (VEGF)-A and VEGF-C mRNA levels in tumors were similar in the control and pHSVtk/GCV groups. In the second experiment, tumor volume and metastatic parameters were compared for immunocompetent syngeneic mice and immunodeficient athymic mice (without an intact T-cell system) given pHSVtk/GCV therapy. Although tumor volumes were significantly smaller in both syngeneic and athymic mice given pHSVtk/GCV therapy, the inhibition ratios (relative to control mice) were much greater in syngeneic mice than in athymic mice. No suppression of metastasis to the lymph nodes and lungs was observed for athymic mice given pHSVtk/GCV therapy. Our data suggest that HSVtk/GCV suicide gene therapy exerts an antimetastatic effect via a T-cell-mediated immune response.
Med Mol Morphol 2008 Mar
PMID:Antimetastatic effect of suicide gene therapy for mouse mammary cancers requires T-cell-mediated immune responses. 1847 Jun 79

Blood vessels are required for a tumor to grow and functional lymphatic vessels are required for it to disseminate to lymph nodes. In an attempt to eradicate both the primary tumor and its lymphatic metastasis, we targeted both blood and lymphatic vessels using two different tyrosine kinase inhibitors (TKIs): cediranib and vandetanib, which block vascular endothelial growth factor receptor (VEGFR)-2 and -3 in enzymatic assays. We found that although both cediranib and vandetanib slowed the growth rate of primary tumors and reduced blood vessel density, neither agent was able to prevent lymphatic metastasis when given after tumor cells had seeded the lymph node. However, when given during tumor growth, cediranib reduced the diameters of the draining lymphatic vessels, the number of tumor cells arriving in the draining lymph node, and the incidence of lymphatic metastasis. On the other hand, vandetanib had minimal effect on any of these variables, suggesting that vandetanib did not effectively block VEGFR-3 on lymphatic endothelial cells in our animal model. Collectively, these data indicate that the response of lymphatic vessels to a TKI can determine the incidence of lymphatic metastasis, independent of the effect of the TKI on blood vessels.
Mol Cancer Ther 2008 Aug
PMID:Differential response of primary tumor versus lymphatic metastasis to VEGFR-2 and VEGFR-3 kinase inhibitors cediranib and vandetanib. 1868 59

Sphingosine-1-phosphate receptor 1 (S1P(1)), a receptor for sphingosine-1-phosphate, has been shown to play an important role in the migration, proliferation, and survival of several types of cell including endothelial cells. Given that S1P(1) signaling could serve as a therapeutic target, we evaluate the expression of S1P(1) in formalin-fixed and paraffin-embedded sections from human tissues, using automated immunostainers (Ventana). The specificity of the polyclonal rabbit anti-human S1P(1) antibody used in this study was defined by immunostaining of the vasculature in S1P ( 1 ) ( -/- ) and S1P ( 1 ) ( +/- ) mouse embryos. The antibody stained the newly formed vasculatures ex vivo in a serum-free matrix culture model using rat aortic rings. In human specimens, S1P(1) was strongly expressed on the cell surface membrane of endothelial cells of blood and lymphatic vessels in all tissues examined. The expression of S1P(1) was confirmed by the flow cytometric analysis and real time RT-PCR of an angiosarcoma cell line. This study indicates that S1P(1) can be used as an immunohistochemical marker for human tissue endothelial cells.
J Mol Histol 2008 Oct
PMID:Immunohistochemical detection of sphingosine-1-phosphate receptor 1 in vascular and lymphatic endothelial cells. 1875 70

The chick embryo chorioallantoic membrane (CAM) is an extraembryonic membrane mediating gas and nutrient exchanges until hatching. Since it has a dense capillary network, it has been commonly used in vivo to study both angiogenesis and antiangiogenesis in response to normal tissues and cells, to tumor bioptic specimens and cells, or to soluble factors. During the last 8 years, this assay has been used in over 550 published works. This chapter summarizes current knowledge about the embryological origin of the CAM, morphology of its blood and lymphatic vessels, the use of CAM in the study of tumor angiogenesis and metastasis, angiogenic and antiangiogenic substances. The angiogenic response of CAM to multiple myeloma and neuroblastoma cells and bioptic specimens and their responses to antiangiogenic molecules and the role played by fibroblast growth factor-2 in CAM vascularization have been analyzed in detail. Finally, advantages and limitations of CAM as an experimental model to study angiogenesis and antiangiogenesis are discussed.
Int Rev Cell Mol Biol 2008
PMID:Chick embryo chorioallantoic membrane as a useful tool to study angiogenesis. 1908 37

The field of lymphatic research has benefited enormously from the recent discovery of "marker" proteins that permit not only the identification and quantitation of lymphatic vessels in tissue sections for tumor pathology but also the isolation of primary lymphatic endothelial cells for basic research. This chapter focuses on the use of these markers for the immunohistochemical analysis of lymphangiogenesis in both frozen and paraffin-embedded tissue sections and discusses current protocols and their associated problems.
Methods Mol Biol 2009
PMID:Immunohistochemical methods for measuring tissue lymphangiogenesis. 1930 65

Metastasis is a characteristic trait of most tumour types and the cause for the majority of cancer deaths. Many tumour types, including melanoma and breast and prostate cancers, first metastasize via lymphatic vessels to their regional lymph nodes. Although the connection between lymph node metastases and shorter survival times of patients was made decades ago, the active involvement of the lymphatic system in cancer, metastasis has been unravelled only recently, after molecular markers of lymphatic vessels were identified. A growing body of evidence indicates that tumour-induced lymphangiogenesis is a predictive indicator of metastasis to lymph nodes and might also be a target for prevention of metastasis. This article reviews the current understanding of lymphangiogenesis in cancer anti-lymphangiogenic strategies for prevention and therapy of metastatic disease, quantification of lymphangiogenesis for the prognosis and diagnosis of metastasis and in vivo imaging technologies for the assessment of lymphatic vessels, drainage and lymph nodes.
J Cell Mol Med 2009 Aug
PMID:Lymphangiogenesis and cancer metastasis. 1958 13

During carcinogenesis it is known that growth factors and cytokines from stromal and inflammatory cells from the microenvironment promote angiogenesis and lymphangiogenesis. However, the participation of macrophages and mast cells in these processes is not well understood. The aim of this study was to evaluate the relationship between mast cell and macrophage density with blood and lymphatic vessels in various stages of carcinoma of the uterine cervix. Tissue sections from archival paraffin-embedded samples from cases with cervical intraepithelial neoplasias (CIN) 1, 2, 3, carcinoma in situ, and invasive carcinoma were used. Immunohistochemical staining was done using the following antibodies: anti-LYVE-1; anti-CD31; anti-CD68, and anti-tryptase. Our results showed a significant increase in the number of macrophages in carcinoma in situ, a correlation between lymphatic vessels and macrophages in premalignant lesions CIN 2, and a correlation between mast cells and blood vessels in both CIN 2 and carcinoma in situ. In conclusion, our data underscore the importance of the recruitment of macrophages and mast cells in the development of tumor-associated blood and lymphatic capillaries.
Exp Mol Pathol 2010 Oct
PMID:The role of macrophages and mast cells in lymphangiogenesis and angiogenesis in cervical carcinogenesis. 2059 41

D2-40 has been recently discovered as a lymphatic endothelial cell marker, and some investigators have found that D2-40 is also expressed in myoepithelial cells of salivary gland or breast. In this study, we evaluated D2-40 expression of basal cells and applied D2-40 immunohistochemistry in the combination of P504S, cytokeratin 5, and p63 for ten lesions with atypical small acinar proliferation (ASAP) in initial prostatic needle biopsy. As a result, D2-40 was expressed in basal cells, lymphatic endothelial cells, and some stromal fibroblasts of normal prostatic tissue. Among ten ASAP lesions, the final diagnosis of seven lesions was resolved by combination immunohistochemistry. D2-40 was comparable to cytokeratin 5 and p63 as a basal cell marker, and there were no lesions that failed to provide an accurate final diagnosis using only D2-40 immunohistochemistry without cytokeratin 5 or p63. However, we found some D2-40-positive stromal fibroblasts or D2-40-positive lumen-collapsed lymphatic vessels neighboring atypical glands. Pathologists should pay attention to avoid recognizing these cells as basal cells. In conclusion, the combination of immunohistochemistry of P504S, cytokeratin 5, p63, and D2-40 may contribute to the accurate diagnosis of ASAP in the initial prostatic needle biopsy.
Med Mol Morphol 2010 Sep
PMID:Immunohistochemical application of D2-40 as basal cell marker in evaluating atypical small acinar proliferation of initial routine prostatic needle biopsy materials. 2085 65


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