Evaluation of Angiogenesis with the Expression of VEGF-C and CD34 in Human Colon Cancer

Inda, Ana; García, Marcela Nilda; Andrini, Laura Beatríz; Garcı́a, Adriana; Blanco, Ayelén Melisa; Furnus, Cecilia Cristina; Galletti, Susana; Brandoni, J.; Martínez, Jorge; Prat, Guillermo Daniel; Errecalde, Ana

doi:10.2174/2212796810903030302

Cited by 13 publications

(14 citation statements)

References 21 publications

(24 reference statements)

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“…Although it is unclear why CD34 positivity does not correlate with VEGF levels when the two routes of injection are compared, both routes support the conclusion that IGFBP7 reduces VEGF production compared to controls. It is noteworthy that CD34 has been shown to be a better marker of neoangiogenesis than VEGF in NSCLC [23]. Anti-angiogenic effects of IGFBP7 have been found in other model systems of cancer.…”

Section: Discussionmentioning

confidence: 98%

IGFBP7 reduces breast tumor growth by induction of senescence and apoptosis pathways

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Yang

Amemiya

et al. 2011

Breast Cancer Res Treat

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Insulin-like growth factor binding protein 7 (IGFBP7) has been shown to be a tumor suppressor in a variety of cancers. We previously have shown that IGFBP7 expression is inversely correlated with disease progression and poor outcome in breast cancer. Overexpression of IGFBP7 in MDA-MB-468, a triple-negative breast cancer (TNBC) cell line, resulted in inhibition of growth and migration. Xenografted tumors bearing ectopic IGFBP7 expression were significantly growth-impaired compared to IGFBP7-negative controls, which suggested that IGFBP7 treatment could inhibit breast cancer cell growth. To confirm this notion, 14 human patient primary breast tumors were analyzed by qRTPCR for IGFBP7 expression. The TNBC tumors expressed the lowest levels of IGFBP7 expression, which also correlated with higher tumorigenicity in mice. Furthermore, when breast cancer cell lines were treated with IGFBP7, only the TNBC cell lines were growth inhibited. Treatment of NOD/SCID mice harboring xenografts of TNBC cells with IGFBP7 systemically every 3-4 days inhibited tumorigenesis, with associated anti-angiogenic effects, together with increased apoptosis. Upon examining the mechanism of IGFBP7-mediated growth inhibition in TNBC cells, we found that cells not only were arrested in G1 phase of the cell cycle but also underwent senescence as a result of treatment with IGFBP7. Interestingly, IGFBP7 treatment was also associated with strong activation of the stress-associated p38 MAPK pathway, together with upregulation of p53 and the cyclin-dependent protein kinase (CDK) inhibitor, p21(cip1). Prolonged treatment of cells with IGFBP7 resulted in increased cell death, marked by an increase in apoptotic cells and associated cleaved PARP. This is the first study showing that exogenous IGFBP7 inhibits TNBC cell growth both in vitro and in vivo. Taken together, these results suggest IGFBP7 treatment might have therapeutic potential for TNBC.

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Section: Discussionmentioning

confidence: 98%

IGFBP7 reduces breast tumor growth by induction of senescence and apoptosis pathways

Benatar

Yang

Amemiya

et al. 2011

Breast Cancer Res Treat

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“…An important process necessary for tumour progression, invasion and metastasis is angiogenesis. VEGF, which is the most effective pro-angiogenetic factor identified to date (Inda et al, 2007), is highly expressed in PCa and implicated in PCa initiation and metastasis (El-Gohary et al, 2007;Fukuda et al, 2007). Interestingly, hypoxia not only increases the expression of VEGF but also induces SDF-1 expression, suggesting that VEGF might mediate the up-regulation of SDF-1 under hypoxic conditions (Kijowski et al, 2001;Oda et al, 2006;Hao et al, 2007;Liang et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Regulation of VEGF, MMP-9 and metastasis by CXCR4 in a prostate cancer cell line

et al. 2011

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To investigate the mechanisms involved in PCa (prostate cancer) metastasis and CXCR4 (CXC chemokine receptor-4)-mediated VEGF (vascular endothelial growth factor) and MMP-9 (matrix metalloproteinase-9) expression, we used lentivirus-mediated RNAi (RNA interference) to reduce the expression of CXCR4 in a PCa cell line. We found that the silencing of CXCR4 led to a significant down-regulation of VEGF and MMP-9 at both the mRNA and protein levels compared with the control in vitro. Using an animal model, we confirmed that CXCR4 silencing via subcutaneous injection could reduce tumour growth as well as inhibit metastasis, particularly bone metastasis, of PCa. Using in vivo immunohistochemistry, we also found that the expression of VEGF and MMP-9 were reduced by the knockdown of CXCR4 in the primary tumours of mice. Collectively, our results indicate that CXCR4 plays an important role in PCa metastasis through the up-regulation of VEGF and MMP-9. These findings may aid future intervention strategies.

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“…It was purified from the medium of bovine pituitary gland folliculostellate cells, and its activity was detected in the mitosis induction of vascular endothelial cells [6]. VEGF is one of the most active and specific vascular growth factors and induces the proliferation, migration, and differentiation of endothelial cells [7]. VEGF can interact with VEGF receptors (VEGFR) to trigger receptor tyrosine kinase activation, and activate the downstream phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway [8], one of the most important signaling pathways in vivo, which is involved in the processes of growth, differentiation, and metabolism [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Vascular endothelial growth factor induces multidrug resistance-associated protein 1 overexpression through phosphatidylinositol-3-kinase /protein kinase B signaling pathway and transcription factor specificity protein 1 in BGC823 cell line

Li¹,

Wu²,

Gong³

et al. 2013

ABBS

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Multidrug resistance (MDR) is one of the most important causes of chemotherapy failure and carcinoma recurrence. But the roles of the MDR-associated protein MRP1 in MDR remain poorly understood. Vascular endothelial growth factor (VEGF), one of the most active and specific vascular growth factors, plays a significant role in proliferation, differentiation, and metastasis of cancers. To explore the effect of VEGF on the expression of MRP1, we used recombinant human VEGF to stimulate K562 and BGC-823 cell lines. Quantitative real-time polymerase chain reaction and western blot analysis showed that the expression of MRP1 at both mRNA and protein levels was increased. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide results also showed that VEGF significantly enhanced the IC 50 of the cells treated with adriamycin. To explore the underlying regulatory mechanisms, we constructed MRP1 promoter and the luciferase reporter gene recombinant vector. The luciferase reporter gene assay showed that the activity of the MRP1 promoter was markedly increased by VEGF stimulation, while LY294002, an inhibitor of the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, reduced this effect. Transcription factor specificity protein 1 (SP1) binding site mutation partially blocked the up-regulation of MRP1 promoter activity by VEGF. In summary, our results demonstrated that VEGF enhanced the expression of MRP1, and the PI3K/Akt signaling pathway and SP1 may be involved in this modulation.

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Evaluation of Angiogenesis with the Expression of VEGF-C and CD34 in Human Colon Cancer

Cited by 13 publications

References 21 publications

IGFBP7 reduces breast tumor growth by induction of senescence and apoptosis pathways

IGFBP7 reduces breast tumor growth by induction of senescence and apoptosis pathways

Regulation of VEGF, MMP-9 and metastasis by CXCR4 in a prostate cancer cell line

Vascular endothelial growth factor induces multidrug resistance-associated protein 1 overexpression through phosphatidylinositol-3-kinase /protein kinase B signaling pathway and transcription factor specificity protein 1 in BGC823 cell line

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