Vascular endothelial growth factor gene and protein: strong expression in thyroiditis and thyroid carcinoma

Angiogenesis is implicated in several pathological conditions, such as inflammation and tumor growth. Vascular endothelial growth factor (VEGF), also known as vascular permeability factor, is a potent stimulator of endothelial cell proliferation in vitro and in vivo. The present work aimed to compare VEGF expression in human normal thyroid glands, thyroiditis tissue and thyroid carcinomas using immunohistochemistry and in situ hybridization (ISH). Both chronic lymphocytic thyroiditis and differentiated thyroid carcinomas were found to strongly express VEGF mRNA and encode larger amounts of VEGF than normal thyroid tissue as attested by a VEGF immunostaining score. In addition, tumor samples from patients with metastases showed a higher immunostaining score than their non-metastatic counterparts (P<0.05). Carcinomas with the greatest contents of VEGF mRNA and VEGF protein had the most intense mitogenic activity. Special focus on endothelial cells showed intense mitogenic activity in neoplastic tissues in contrast to the total quiescence of endothelial cells in non-tumoral tissues. An intense VEGF production by differentiated thyroid carcinoma, attested either by a higher immunostaining score or a strong VEGF mRNA expression using ISH, could be a promising marker of tumor aggressiveness and may also be useful as a predictor of metastatic potential.

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Expression of Vascular Endothelial Growth Factor in Human Umbilical Vein Endothelial Cells Stimulated with Interleukin-1α

Thrombosis and Haemostasis ◽

10.1055/s-0037-1613948 ◽

2000 ◽

Vol 83 (06) ◽

pp. 949-955 ◽

Cited By ~ 34

Author(s):

Hiroyuki Itaya ◽

Satoki Nasu ◽

Hidemi Yoshida ◽

Yuki Matsubara ◽

Koji Fujimoto ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Endothelial Cells ◽

Growth Factor ◽

Umbilical Vein ◽

Vascular Endothelial ◽

Vegf Mrna ◽

Interleukin 1Α ◽

Umbilical Vein Endothelial Cells ◽

Endothelial Growth Factor ◽

Vegf Protein

SummaryVascular endothelial growth factor (VEGF) is a specific mitogen for endothelial cells. We studied the production of VEGF by human umbilical vein endothelial cells (HUVEC) and smooth muscle cells (SMC) in response to the stimulation with interleukin-1α (IL-1α). HUVEC expressed VEGF mRNA in response to IL-1α in doseand time-dependent manners. In HUVEC VEGF protein was detected only in cell lysates whereas in SMC most of the VEGF protein was detected in the conditioned medium. Immunofluorescent staining also confirmed the cell-associated VEGF in HUVEC. IL-1α also induced the expression of mRNA for IL-1α itself in HUVEC. Cycloheximide treatment of HUVEC slightly inhibited the IL-1α-induced expression of VEGF mRNA, and IL-1α may mediate, at least in part, VEGF expression in response to IL-1α. The growth of HUVEC stimulated with IL-1α was inhibited by a neutralizing antibody against VEGF. We conclude that IL-1α and VEGF may play an important role in autocrine growth regulation of HUVEC.

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Expression of Vascular Endothelial Growth Factor in Human Monocyte/Macrophages Stimulated with Lipopolysaccharide

Thrombosis and Haemostasis ◽

10.1055/s-0037-1612921 ◽

2001 ◽

Vol 85 (01) ◽

pp. 171-176 ◽

Cited By ~ 48

Author(s):

Hiroyuki Itaya ◽

Hidemi Yoshida ◽

Masayuki Koyama ◽

Sohei Suzuki ◽

Kei Satoh ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Endothelial Cells ◽

Growth Factor ◽

Map Kinase ◽

Human Monocyte ◽

P38 Map Kinase ◽

Vascular Endothelial ◽

Vegf Expression ◽

Vegf Mrna ◽

Endothelial Growth Factor

SummaryVascular endothelial growth factor (VEGF) is a mitogen for endothelial cells. We have studied the production of VEGF by human macrophages in response to lipopolysaccharide (LPS). Macrophages stimulated with LPS expressed VEGF mRNA and protein in concentration- and time-dependent manners. The LPS-induced expression of VEGF was inhibited by cycloheximide pretreatment, which suggested that synthesis of certain factor(s) is required for the LPS activity. The induction of VEGF was also suppressed by SB203580, an inhibitor of p38 mitogen-activated protein (MAP) kinase. These results suggest that the LPS-induced VEGF expression depends on the p38-mediated expression of c-Jun, which constitutes the AP-1 complex and binds to the AP-1 site in the VEGF promoter. Pretreatment of the cells with dexamethasone did not affect the LPS-induced upregulation of VEGF mRNA but strongly inhibited VEGF protein production, and the involvement of posttranscriptional regulation on VEGF expression by dexamethasone was suggested. The conditioned medium of LPS-stimulated macrophages enhanced the growth of cultured endothelial cells and it was inhibited by an antibody against VEGF. We conclude that macrophages produce VEGF in response to the stimulation with LPS, which may be partly mediated by the p38 MAP kinase pathway.

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The Prognostic Role of Vascular Endothelial Growth Factor-A Expression in Thyroid Carcinomas

Folia Medica ◽

10.2478/folmed-2018-0059 ◽

2019 ◽

Vol 61 (1) ◽

pp. 61-68

Author(s):

Zana Vela-Gaxha ◽

Labinot Shahini ◽

Suzana Manxhuka-Kerliu

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Thyroid Carcinoma ◽

Thyroid Tissue ◽

Endocrine Tumors ◽

Vascular Endothelial ◽

Thyroid Carcinomas ◽

Endothelial Growth Factor ◽

Benign Thyroid

Abstract Background: Thyroid carcinomas are the most common endocrine tumors – they account for 95% of all endocrine tumors. Thyroid carcinomas are more vascular than normal thyroid tissue. For the tumor to grow and subsequently metastasize it is crucial that it induces angiogenesis. This requires a change in the balance between certain angiogenic factors such as the vascular endothelial growth factor-A (VEGF-A) and the inhibitors of angiogenesis. The aim of this study was to evaluate the role of VEGF-A expression in thyroid carcinomas. Materials and methods: The present prospective study included 80 cases, of which 60 were patients with thyroid cancer including papillary, follicular, medullary and anaplastic carcinoma, and 20 patients (controls) with benign thyroid tissue (thyroid goiter). All cases were examined using the immunohistochemical staining for VEGF-A. Results: VEGF-A expression in thyroid carcinoma was significantly higher than in benign thyroid tissues (p<0.001). VEGF-A expression values in thyroid carcinoma did not associate with tumor necrosis degree (p=1.000). Furthermore, VEGF-A expression values in thyroid carcinoma were not associated with other prognostic factors such as tumor hemorrhage, angioinvasion, atypical mitosis, and lymphatic invasion. Conclusion: Our data showed that the VEGF-A expression is upregulated in thyroid cancers compared with benign thyroid tissue. Therefore, it would be useful to perform IHC staining for VEGF-A expression as a valuable diagnostic tool in TC.

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Angiogenesis in the Human Corpus Luteum: Localization and Changes in Angiopoietins, Tie-2, and Vascular Endothelial Growth Factor Messenger Ribonucleic Acid1

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.85.11.6942 ◽

2000 ◽

Vol 85 (11) ◽

pp. 4302-4309 ◽

Cited By ~ 3

Author(s):

Christine Wulff ◽

Helen Wilson ◽

Pawlina Largue ◽

W. Colin Duncan ◽

David G. Armstrong ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Endothelial Cells ◽

Growth Factor ◽

Corpus Luteum ◽

Luteal Phase ◽

Corpora Lutea ◽

Vascular Endothelial ◽

Vegf Mrna ◽

Messenger Ribonucleic Acid ◽

Endothelial Growth Factor

In the menstrual cycle, extensive angiogenesis accompanies luteinization. During luteolysis, endothelial cells die, whereas in a conceptual cycle, the corpus luteum (CL) persists, and endothelial cell survival is extended. A main stimulator for angiogenesis is vascular endothelial growth factor (VEGF), while the angiopoietins (Ang-1 and Ang-2) may be important modulators. The aim of this study was to investigate the localization of Ang-1, Ang-2, their common receptor Tie-2, and VEGF messenger ribonucleic acid (mRNA) at the different stages of the functional luteal phase and after rescue by hCG. Ang-1 mRNA was uniformly expressed at a low level throughout the CL. The signal was highest during the early luteal phase. In contrast, Ang-2 mRNA expression was localized strongly to individual granulosa and thecal luteal and endothelial cells. Administration of hCG was associated with an increase in the Ang-2 mRNA area of expression and grain density in individual luteal and endothelial cells. The Tie-2 receptor mRNA was localized in endothelial cells, and the area of expression was highest during the early luteal phase and during luteal rescue. VEGF mRNA was found exclusively in granulosa luteal cells, and the area of expression was highest in corpora lutea during simulated pregnancy. These results begin to characterize the molecular regulation of the divergent processes involved in luteal angiogenesis during luteinization, luteolysis, and rescue in the human and imply that the angiopoietins are involved during the initial angiogenic phase and in luteal rescue.

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Glomerular endothelial cells in culture express and secrete vascular endothelial growth factor

AJP Renal Physiology ◽

10.1152/ajprenal.1994.266.1.f81 ◽

1994 ◽

Vol 266 (1) ◽

pp. F81-F88 ◽

Cited By ~ 3

Author(s):

K. Uchida ◽

S. Uchida ◽

K. Nitta ◽

W. Yumura ◽

F. Marumo ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Endothelial Cells ◽

Growth Factor ◽

Protein Kinase ◽

Mrna Abundance ◽

Vascular Endothelial ◽

Vegf Expression ◽

Vegf Mrna ◽

Glomerular Endothelial Cells ◽

Endothelial Growth Factor

Vascular endothelial growth factor (VEGF) is a specific growth factor for endothelial cells, and its abundant expression has been reported in kidney glomeruli. In this study, we focused on glomerular endothelial cells (GEN) as a possible source of VEGF secretion and sought to uncover a potential autocrine role of VEGF for GEN. Ribonuclease protection assay demonstrated VEGF mRNA expression in cultured GEN, and 46-kDa VEGF protein was detected in the conditioned medium by immunoblot analysis using polyclonal antibody raised against the NH2-terminal portion of VEGF. Removal of fetal bovine serum (FBS) from the culture medium for 2 h decreased VEGF mRNA abundance, which was restored by the readdition of FBS (10%) within 2 h. The effect of FBS was completely abolished by protein kinase inhibitor H-7 (10 microM), suggesting that FBS-stimulated VEGF mRNA induction involves activation of protein kinases. The treatment of GEN with 10(-7) M 12-O-tetradecanoylphorbol-13-acetate (TPA) increased the VEGF mRNA abundance fivefold, supporting the idea that VEGF expression is regulated by protein kinase C. [3H]thymidine incorporation into GEN treated with TPA (10(-7) M) was inhibited by neutralizing antibody for VEGF. Thus VEGF was identified as an autocrine growth factor for GEN in vitro. Its physiological role might be the regulation of GEN proliferation, and the induction of VEGF expression by FBS and TPA suggests its involvement in the response of glomerular capillary endothelial cells to injury in certain pathophysiological states.

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