Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.5 (5'-nucleotidase)
 3,167 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A family of growth factors highly specific for endothelial cells was identified more than 10 years ago, in which the receptor of vascular endothelial growth factor C (VEGFR-3) is implicated in the regulation of lymphatic development and regeneration. Comparative studies on the lymphatic network and lymphangiogenesis have been done mainly using combined 5'-nucleotidase (5'-Nase) enzyme and VEGFR-3 immunohistochemical approaches in adult and fetal gastric walls. Developing lymphatic networks represented fewer blind ends and branches than mature networks in whole-mount preparations. Many circular lymphatic-like structures exhibited VEGFR-3 expression and weak 5'-Nase activity in the early embryonic stage, showing visible morphological properties in the lymphatic endothelium. These newly formed lymphatics showed an obvious accumulation in the submucosa and serosa and a variation in the intensity of VEGFR-3 binding to endothelial cells among samples. A reaction product for anti-VEGFR-3 was found on the luminal surface of endothelial cells and on the membrane of some organelles and intraluminal lymphocytes. These findings indicate that an active proliferating feature of the clustered developing lymphatics may create a favorable environment for their sprouting and growth, which may serve as a functional requirement for lymph drainage in the region.
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PMID:Lymphatic network and lymphangiogenesis in the gastric wall. 1258 61

Lymphagenesis in gastrointestinal tumors is not well described. To clarify its presence and regulation, we assessed the microlymphatic count (MLC) in colorectal cancer patients. Lymphatic vessels were evaluated by enzyme-histochemistry for 5'-nucleotidase (5'-NA). Since vascular endothelial growth factor (VEGF)-C is reportedly associated with lymphagenesis, the expression of VEGF-C protein was immunohistochemically assessed by the catalyzed signal amplification (CSA) method. MLC of peritumoral lesions was significantly higher than that of non-cancer and intratumoral lesions (p<0.01); it increased where VEGF-C was highly expressed (p<0.01) and increased with the depth of invasion in peritumoral lesions. These results indicate significant findings at peritumoral lesion: that lymphagenesis may be elicited by tumor spread; that VEGF-C expression is associated with lymphagenesis and is a potent factor stimulating lymphagenesis.
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PMID:Lymphagenesis correlates with expression of vascular endothelial growth factor-C in colorectal cancer. 1279 49

Lymphatic spread of colorectal cancer cells to regional lymph nodes is one of the early events in metastatic cancer, and is often associated with distant metastatic spread and a poor prognosis. This study examined lymphangiogenic factors, and in particular a panel of newly discovered lymphangiogenic markers, in colorectal cancer tissues from a cohort of patients. Paired samples (background normal mucosa and cancer) of colon tissue were obtained from patients with colorectal cancer. The expression and levels of the VEGF-C and VEGF-D cytokines, the VEGF receptors VEGFR-2 and VEGFR-3, and newly described lymphatic endothelial markers, LYVE-1, Prox-1, podoplanin and 5'-nucleotidase were assessed. RNA was extracted from the frozen colon tissues. The level of expression for each factor/marker was determined using RT-PCR and quantified using a real-time quantitative PCR (RT-QPCR) technique, with respective cloned cDNA plasmids as internal standards. VEGF-D was expressed to a significantly higher degree in the colon tumour tissues. There was no significant difference between the expression levels for both VEGF-C and its receptor, VEGFR-2, in background and cancer tissues. However, levels of the VEGFR-3 receptor were found to be significantly higher in colon cancer than the normal background tissues. LYVE-1 levels were below detection in most cases. There was a significant increase in the degree of Prox-1 and 5'-nucleotidase expression in colon cancer tissue. Podoplanin expression was also increased in the cancer samples. These markers indicate an increase in lymphangiogenesis in colon cancer, and may therefore have prognostic value for colon cancer patients.
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PMID:Quantitative analysis of lymphangiogenic markers in human colorectal cancer. 1285 6

Regeneration of lymphatic vessels after transection of the muscle coat in the rat jejunum was studied by histochemical methods. The lymphatic regrowth occurred behind the regeneration of blood vessels. Enzyme histochemistry for 5'-nucleotidase (5'-Nase) demonstrated the manner of lymphatic regrowth, which was essentially attributed to vascular sprouting from preexisting lymphatics, and structural changes of the endothelial cells indicating their high migratory potential. The lymphatic regeneration progressively advanced with vascular maturation throughout the experimental period. The expression of 5'-Nase in the regenerating lymphatics was increased in proportion to their growth. VEGF-C, a highly specific lymphangiogenic factor, was highly expressed in a subpopulation of interstitial cells, being close to the regrowing lymphatics with immunoreactivity of its receptor, VEGFR-3, in the regenerative area. The present findings suggest that transection of the intestinal muscle coat affords a useful experimental model for the investigation of lymphatic regeneration in tissue repair and that the interstitium may play a crucial role in lymphangiogenesis.
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PMID:Regrowth of lymphatic vessels following transection of the muscle coat in the rat small intestine. 1506 37

Endothelial progenitor cells (EPCs) play an important role in postnatal neovascularization. However, it is poorly understood whether EPCs contribute to lymphangiogenesis. Here, we assessed differentiation of a novel population of EPCs towards lymphatic endothelial cells and their lymphatic formation. CD34(+) VEGFR-3(+) EPCs were isolated from mononuclear cells of human cord blood by fluorescence-activated cell sorting. These cells expressed CD133 and displayed the phenotype of the endothelial cells. Cell colonies appeared at 7-10 days after incubation. The cells of the colonies grew rapidly and could be repeatedly subcultured. After induction with VEGF-C for 2 weeks, CD34(+) VEGFR-3(+) EPCs could differentiate into lymphatic endothelial cells expressing specific markers 5'-nucleotidase, LYVE-1 and Prox-1. The cells also expressed hyaluronan receptor CD44. The differentiated cells had properties of proliferation, migration and formation of lymphatic capillary-like structures in three-dimensional collagen gel and Matrigel. VEGF-C enhanced VEGFR-3 mRNA expression. After interfering with VEGFR-3 siRNA, the effects of VEGF-C were diminished. These results demonstrate that there is a population of CD34(+) VEGFR-3(+) EPCs with lymphatic potential in human cord blood. VEGF-C/VEGFR-3 signalling pathway mediates differentiation of CD34(+) VEGFR-3(+) EPCs towards lymphatic endothelial cells and lymphangiogenesis. Cord blood-derived CD34(+) VEGFR-3(+) EPCs may be a reliable source in transplantation therapy for lymphatic regenerative diseases.
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PMID:CD34+ VEGFR-3+ progenitor cells have a potential to differentiate towards lymphatic endothelial cells. 2445 Apr 75