scholarly journals Small Molecule Chloropyramine Hydrochloride (C4) Targets the Binding Site of Focal Adhesion Kinase and Vascular Endothelial Growth Factor Receptor 3 and Suppresses Breast Cancer Growth in Vivo

2009 ◽  
Vol 52 (15) ◽  
pp. 4716-4724 ◽  
Author(s):  
Elena V. Kurenova ◽  
Darell L. Hunt ◽  
Dihua He ◽  
Andrew T. Magis ◽  
David A. Ostrov ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Focal Adhesion ◽  
Growth Factor Receptor ◽  
Cancer Growth ◽  
Vascular Endothelial ◽  
Breast Cancer Growth ◽  
Endothelial Growth Factor

Glipizide Combined with ANP Suppresses Breast Cancer Growth and Metastasis by Inhibiting Angiogenesis through VEGF/VEGFR2 Signaling

2021 ◽  
Vol 21 ◽  
Author(s):  
Guanquan Mao ◽  
Shuting Zheng ◽  
Jinlian Li ◽  
Xiaohua Liu ◽  
Qin Zhou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Natriuretic Peptide ◽  
Umbilical Vein ◽  
Tube Formation ◽  
Cancer Growth ◽  
Vascular Endothelial ◽  
Breast Cancer Growth ◽  
Endothelial Growth Factor

Background: Breast cancer is one of the most common cancers worldwide among women, and angiogenesis has an important effect on its growth and metastasis. Glipizide, which is a widely used drug for type 2 diabetes mellitus, has been reported to inhibit tumor growth and metastasis by upregulating the expression of natriuretic peptide receptor A (NPRA). Atrial natriuretic peptide (ANP), the receptor of NPRA, plays an important role in angiogenesis. The purpose of this study was to explore the effect of glipizide combined with ANP on breast cancer growth and metastasis. Methods: To investigate the effect of glipizide combined with ANP on breast cancer, glipizide, ANP or glipizide combined with ANP was intraperitoneally injected into MMTV-PyMT mice. To explore whether the anticancer efficacy of glipizide combined with ANP was correlated with angiogenesis, a tube formation assay was performed. Results: Glipizide combined with ANP was found to inhibit breast cancer growth and metastasis in MMTV-PyMT mice, which spontaneously develop breast cancer. Furthermore, the inhibitory effect of ANP combined with glipizide was better than that of glipizide alone. ANP combined with glipizide significantly inhibited tube formation of human umbilical vein endothelial cells (HUVECs) by suppressing vascular endothelial growth factor (VEGF)/VEGFR2 (vascular endothelial growth factor receptor 2) signaling. Conclusions: These results demonstrate that glipizide combined with ANP has a greater potential than glipizide alone to be repurposed as effective agents for the treatment of breast cancer by targeting tumor-induced angiogenesis.

Mice overexpressing placenta growth factor exhibit increased vascularization and vessel permeability

2002 ◽  
Vol 115 (12) ◽  
pp. 2559-2567 ◽  
Author(s):  
Teresa Odorisio ◽  
Cataldo Schietroma ◽  
M. Letizia Zaccaria ◽  
Francesca Cianfarani ◽  
Cecilia Tiveron ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Adult Life ◽  
Growth Factor Receptor ◽  
Vascular Endothelial ◽  
Placenta Growth Factor ◽  
Vessel Permeability ◽  
Exact Function ◽  
Endothelial Growth Factor

Placenta growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family, comprising at least five cytokines specifically involved in the regulation of vascular and/or lymphatic endothelium differentiation. Several lines of evidence indicate a role for PlGF in monocyte chemotaxis and in potentiating the activity of VEGF, but the exact function of this cytokine is not fully understood. To define the biological role of PlGF in vivo, we have produced a transgenic mouse model overexpressing this factor in the skin by using a keratin 14 promoter cassette. Our data indicate that PlGF has strong angiogenic properties in both fetal and adult life. PlGF overexpression results in a substantial increase in the number,branching and size of dermal blood vessels as well as in enhanced vascular permeability. Indeed, intradermally injected recombinant PlGF was able to induce vessel permeability in wild-type mice. The analysis of vascular endothelial growth factor receptor 1/flt-1 and vascular endothelial growth factor receptor 2/flk-1 indicates that the two receptors are induced in the skin endothelium of transgenic mice suggesting that both are involved in mediating the effect of overexpressed PlGF.

scholarly journals Vascular Endothelial Growth Factor Receptor-2 Expression Is Induced by 17β-Estradiol in ZR-75 Breast Cancer Cells by Estrogen Receptor α/Sp Proteins

Endocrinology ◽  
2006 ◽  
Vol 147 (7) ◽  
pp. 3285-3295 ◽  
Author(s):  
Kelly J. Higgins ◽  
Shengxi Liu ◽  
Maen Abdelrahim ◽  
Kyungsil Yoon ◽  
Kathryn Vanderlaag ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Chromatin Immunoprecipitation ◽  
Breast Cancer Cells ◽  
Growth Factor Receptor ◽  
Vascular Endothelial ◽  
Rich Region ◽  
17Β Estradiol ◽  
Endothelial Growth Factor

Vascular endothelial growth factor receptor-2 kinase insert domain receptor (VEGFR2/KDR) is critical for angiogenesis, and VEGFR2 mRNA and protein are expressed in ZR-75 breast cancer cells and induced by 17β-estradiol (E2). Deletion analysis of the VEGFR2 promoter indicates that the proximal GC-rich region is required for both basal and hormone-induced transactivation, and mutation of one or both of the GC-rich motifs at −58 and −44 results in loss of transactivation. Electrophoretic mobility shift and chromatin immunoprecipitation assays show that Sp1, Sp3, and Sp4 proteins bind the GC-rich region of the VEGFR2 promoter. Results of the chromatin immunoprecipitation assay also demonstrate that ERα is constitutively bound to the VEGFR2 promoter and that these interactions are not enhanced after treatment with E2, whereas ERα binding to the region of the pS2 promoter containing an estrogen-responsive element is enhanced by E2. RNA interference studies show that hormone-induced activation of the VEGFR2 promoter constructs requires Sp3 and Sp4 but not Sp1, demonstrating that hormonal activation of VEGFR2 involves a nonclassical mechanism in which ERα/Sp3 and ERα/Sp4 complexes activate GC-rich sites where Sp proteins but not ERα bind DNA. These results show for the first time that Sp3 and Sp4 cooperatively interact with ERα to activate VEGFR2 and are in contrast to previous results showing that several hormone-responsive genes are activated by ERα/Sp1 in breast cancer cell lines.

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