Angiopoietins(ANGPT) and their endothelial cell-specific tyrosine kinase receptors TEK are the major regulators of blood vessels angiogenesis under physiological and pathologic conditions. ANGPT1 is essentially involved in maturation, stabilization, and remodeling of blood vessels through inducing TEK autophosphorylation, promoting endothelial cell migration and survival. Instead, ANGPT2 appears to act as a natural antagonist of ANGPT1, it can activate vascular remodeling with the presence of vascular endothelial growth factor(VEGF) or regress frank blood vessels under the absence of VEGF. High expression of angiopoietins and TEK is often detected in tumor tissues. Many studies showed that disrupting the ANGPT/TEK receptor pathway could inhibit the growth of a number of murine tumors and human tumors. Thus, it is possible that inhibitors targeting the ANGPT/TEK pathway will have broad clinical utility to treatment of cancer.
Angiopoietin-1 ; physiology ; Angiopoietin-2 ; physiology ; Angiopoietins ; physiology ; Humans ; Neovascularization, Physiologic ; physiology ; Receptor, TIE-2 ; physiology

PURPOSE: Angiopoietin-1 (Ang-1) plays a crucial role in vascular and hematopoietic development, mainly through its cognate receptor, Tie-2. Increased levels of Ang-2 have been shown to be correlated with abnormal tumor angiogenesis in several malignancies. Hence, we estimated the increased expression of Ang-2 relative to Ang-1 in patients with colorectal cancer and correlated our finding with prognosis in order to investigate the relationships between the expressions of Ang-1/Ang-2/Tie-2 receptor and the clinical parameters or overall survival of such patients. METHODS: We retrospectively analyzed 114 tissue samples from patients with colorectal cancer by using immunohistochemistry (IHC) to examine Ang-1, Ang-2, and Tie-2 expressions and to investigate the relationship between those expressions and clinical parameters or overall survival of such patients. A Western blot analysis was used for Ang-2 expression. RESULTS: IHC staining showed a link between Ang-1 and Tie-2 (P = 0.018), as well as meaningful correlations between Ang-2 and Tie-2 receptor (P = 0.022) and between lymph-node metastasis and Ang-2 (P = 0.025). The stronger the IHC staining for Ang-2 expression was, the shorter the cumulative survival was (P = 0.016). CONCLUSION: A relationship was found to exist between Ang-2 and Tie-2 expressions. The Ang-2 was correlated with lymph-node metastasis, and high expression of Ang-2 was indicative of poor overall survival. These findings suggest that Ang-2 is a useful prognostic marker in the management of patients with colorectal cancer. In addition, we suggest that Ang/Tie-2 signaling plays an important role in the progression of colorectal cancer.
Angiopoietin-1* ; Angiopoietin-2* ; Angiopoietins ; Blotting, Western ; Colorectal Neoplasms* ; Humans ; Immunohistochemistry ; Neoplasm Metastasis ; Prognosis ; Receptor, TIE-2* ; Retrospective Studies

OBJECTIVETo observe the expression of angiopoietins in oral squamous cell carcinoma and relationship between the expression of angiopoietins and pathologic classification.

METHODSThe expression of Ang-1 and Ang-2 protein in samples from 42 oral squamous cell carcinoma and 16 oral normal mucosa were detected by immunohistochemical technique.

RESULTSThe expression of Ang-1 and Ang-2 was found in both oral squamous cell carcinoma and normal control. It was found Ang-1 expression alike in oral squamous cell carcinoma and control (P > 0.05). Ang-2 expressed at low level in control while strongly positive in oral squamous cell caroinoma and the level of Ang-2 expression in oral squamous cell caroinoma was related to pathologic classification (P < 0.05).

CONCLUSIONAng-2 expression in oral squamous cell carcinoma is related to angiogenesis and pathological classification, which is probably involved in angiogenesis regulation, promotes the development and metastasis of oral squamous cell carcinoma.

Angiopoietin-1 ; Angiopoietin-2 ; Angiopoietins ; Carcinoma, Squamous Cell ; Humans ; Male ; Middle Aged ; Mouth Mucosa ; Mouth Neoplasms ; Neoplasms ; Neovascularization, Pathologic

PURPOSE: It has been reported that angiopoietins and Tie-2 receptor play an important role in the maintenance of glomerular filtration barrier in various glomerulonephritis models. We studied the role of angiopoietins on renal injury in diabetes. METHODS: In this study, we examined the changes of angiopoietin-1, angiopoietin-2, Tie-2 receptor, and nephrin expression in the experimental diabetic nephropathy and also determined whether these changes were modified by renoprotective intervention by angiotensin II receptor blocker, alpha-lipoic acid, and peroxisome proliferator activated receptor (PPAR)-agonist. RESULTS: A marked increase in urinary albumin excretion and glomerular volume was observed in diabetic rats. Renal angiopoietin-2 and Tie-2 receptor expression were significantly higher in diabetic rats than in the control groups, with a significant reduction in renal angiopoietin-2 expression, albuminuria, and renal hypertrophy in angiotensin II receptor blocker-treated diabetic rats. And there was a significant reduction in renal Tie-2 expression and renal hypertrophy in alpha-lipoic acid-treated and PPAR-gamma agonist-treated diabetic rats. CONCLUSION: These results demonstrate that the dysregulation of angiopoietins and Tie-2 receptor can lead to renal hypertrophy and albuminuria. Angiotensin II receptor blocker, alpha-lipoic acid, and PPAR-gamma agonist attenuated these changes in angiopoietins and/or Tie-2 expression and prevented the development of albuminuria and renal hypertrophy in vivo.
Albuminuria ; Angiopoietin-1 ; Angiopoietin-2 ; Angiopoietins* ; Animals ; Diabetic Nephropathies* ; Glomerular Filtration Barrier ; Glomerulonephritis ; Hypertrophy ; Peroxisomes ; Rats ; Receptor, TIE-2 ; Receptors, Angiotensin ; Thioctic Acid

Angiopoietin-1 ; chemistry ; physiology ; Angiopoietin-2 ; chemistry ; physiology ; Angiopoietins ; physiology ; Animals ; Cardiovascular Diseases ; therapy ; Embryonic and Fetal Development ; Humans ; Neoplasms ; blood supply ; Receptor, TIE-2 ; chemistry ; physiology ; Signal Transduction

BACKGROUND: The Angiopoietin-1 (Ang1), Angiopoietin-2 (Ang2) and Tie2 have essential role in angiogenesis in development. Ang1 and Ang2 are ligands which binds to their receptor, Tie2. METHODS: Expression of these proteins was sought during mouse kidney maturation from embryonic day 16 (E16) to 28 days postnatal (P28). RESULTS: Using RNase protection assay and Western blot, these three molecules were expressed throughout the experimental period with peak levels at P28 (Ang1), P14 (Ang2) and P7 (Tie2). By immunohistochemical analysis, Ang1 protein was found to localize to condensing renal mesenchymal cells, and tubules. Ang2 proteins were detected in differentiating outer medullary tubules and the vasa recta bundle area. Tie2 protein was detected in a portion of glomerular tufts and cortical interstitium, and medulla including vessels in the vasa recta. CONCLUSIONS: These data suggest that Ang1, Ang2 and Tie2 proteins are expressed in renal development.
Angiopoietin-1* ; Angiopoietin-2* ; Animals ; Blotting, Western ; Kidney* ; Ligands ; Mice* ; Receptor, TIE-2 ; Ribonucleases

Minimal change disease (MCD) is a common pathological type of nephrotic syndrome. Its main histology is the fusion of podocyte foot process. The pathogenesis of MCD is not clear, but previously it was thought to be related to immune mechanism. In recent years more studies show that podocyte injury is the key link in the pathogenesis of MCD. In MCD mouse model and human kidney tissues, the expressions of podocyte slit membrane protein-nephrin and podocin, skeleton protein-synaptopodin are decreased, and the expression of synaptopodin is correlated with the response to hormone therapy. In addition, newest studies focused on another two potocyte associated proteins, CD80 and Angiopoietin-like-4. CD80, a T cell stimulating molecule, is expressed in potocyte. Kappa B gene sequences can be activated by external microbes, antigens through acting potocytes, which can induce the upregulation of CD80 expression, cytoskeletal protein damage and the glomerular filtration rate changes, resulting in proteinuria. Angiopoietin-like-4 can be expressed in normal potocytes, but over-expression of angiopoietin-like-4 may injure the GBM charge barrier and induce the foot process fusion, leading to MCD. However, further studies on the factors inducing CD80 and Angiopoietin-like-4 expression, and the interaction between glomerular basement membrane and the two proteins are needed. Based on the mechanism of MCD, NF-kappa B inhibitors and sialylation therapy would be a novel non-immune therapy for MCD.
Angiopoietin-like 4 Protein ; Angiopoietins ; metabolism ; Animals ; B7-1 Antigen ; metabolism ; Disease Models, Animal ; Humans ; Intracellular Signaling Peptides and Proteins ; metabolism ; Kidney ; pathology ; Membrane Proteins ; metabolism ; Mice ; Microfilament Proteins ; metabolism ; NF-kappa B ; metabolism ; Nephrosis, Lipoid ; pathology ; Podocytes ; pathology

OBJECTIVETo investigate the relationship of angiogenesis and the Ang family members/ receptor (Ang/Tie2) in hemangioma.

METHODSExpression of Ang1, Ang2 and the receptor Tie2 was detected with immunohistochemical SP method and RT-PCR method in 17 cases of proliferating hemangioma, 13 involuting cases and 10 cases of normal children skin.

RESULTSThe expression of Ang2 and Tie2 was higher markedly in proliferating hemangiomas than in involuting hemangiomas (P < 0.01), and was rare or negative in normal skin. Expression of Ang1 was rare or negative both in hemangioma and normal skin without significant difference between them (P > 0.05).

CONCLUSIONAng/Tie2 system may play an important role in the proliferating and involuting process of hemangioma.

Angiopoietin-1 ; metabolism ; Angiopoietin-2 ; metabolism ; Child, Preschool ; Hemangioma ; metabolism ; pathology ; Humans ; Infant ; Receptor, TIE-2 ; metabolism

OBJECTIVE: To investigate the mRNA expression of Angiopoietin (Ang)-1 and Ang-2 in ectopic and eutopic endometrium from women with or without endometriosis throughout the menstrual cycle. METHODS: Total RNA was extracted and reverse transcribed into cDNA. The expression of Ang-1 and Ang-2 was examined by quantative competitive PCR (QC PCR) and each result was analyzed by Kruskal- Wallis analysis and Mann-Whitney U-test. RESULTS: The expression of Ang-1 mRNA was statistically significantly higher in endometrium of follicular phase from women with endometriosis compared to that from normal ones in the follicular phase. Endometriotic tissues expressed significantly lower Ang-2 mRNA compared to endometrium from women without endometriosis. CONCLUSION: We suggested that the expression of Ang-1 mRNA could be associated with the pathogenesis of endometriosis and might have a role as neovascularizaton and survival of ectopic endometrium.
Angiopoietin-1* ; Angiopoietin-2* ; DNA, Complementary ; Endometriosis ; Endometrium* ; Female ; Follicular Phase ; Humans ; Menstrual Cycle ; Polymerase Chain Reaction ; RNA ; RNA, Messenger*

OBJECTIVETo study the expression of angiopoietin-1 (Ang-1) and its receptor Tie-2 in multiple myeloma (MM) patients and RPMI8226 cells, and analyze the significance of Ang-1 expression and its relevance to the tumorigenes and development of MM.

METHODSRT-PCR and Western blot were used to detect the expression of Ang-1 and Tie-2 in bone marrow (BM) samples from 112 MM patients and 24 control subjects, and in RPMI8226 cells. The expression levels of Ang-1 in different groups and disease stages were analyzed.

RESULTSThe positive rate and expression level of Ang-1 were significantly higher in MM group than in control group (P < 0.05). The positive rates of Ang-1 were not significantly different between newly diagnosed and relapsed/refractory MM groups, but its expression level was significantly higher in the latter group than in the former group (P < 0.05). Tie-2 was detected only in 12 MM patients and did not in control group and RPMI8226 cells. Microvessel density in BM samples were significantly higher in MM group than in control group (25.21 ± 0.80 vs 5.23 ± 0.20, P < 0.01), and were higher in Ang-1-positive MM group than in Ang-1-negative MM group (32.98 ± 1.70 vs 16.55 ± 1.30, P < 0.05). The positive rates of Ang-1 protein were not significantly different between stage II and stage III MM (52.1% vs 60.9%, P > 0.05), but the expression level of Ang-1 protein was higher in stage III than that in stage II MM (0.40 ± 0.07 vs 0.22 ± 0.04, P < 0.05). In the newly diagnosed MM patients, the positive rate of Ang-1 protein in PD patients was significantly higher than in PR and MR patients (70.0% vs 19.1%, P < 0.01).

CONCLUSIONHigh expression of Ang-1 is found in MM patients and RPMI8226 cells, and its expression is associated with the disease stage, prognosis and targeted therapy of MM.

Angiopoietin-1 ; Humans ; Multiple Myeloma ; metabolism ; Prognosis ; RNA, Messenger ; Receptor, TIE-2