VEGF Exerts an Angiogenesis-Independent Function in Cancer Cells to Promote Their Malignant Progression

Cao, Ying; Guangqi, E; Wang, Enfeng; Pal, Krishnendu; Dutta, Shamit K.; Bar–Sagi, Dafna; Mukhopadhyay, Debabrata

doi:10.1158/0008-5472.can-11-4058

Cited by 119 publications

(102 citation statements)

References 19 publications

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“…It is widely accepted that the higher the expression levels of VEGF-A mRNA, the poorer the breast cancer prognosis (Linderholm et al, 2000). VEGF-A is a pivotal driver of cancer angiogenesis and considered an important therapeutic target in the treatment of malignancy (Cao et al, 2012). The expression of VCAM-1 has been closely associated with oncogenesis, tumor angiogenesis and metastasis in cancer (Ding et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Effects of Differential Distribution of Microvessel Density, Possibly Regulated by miR-374a, on Breast Cancer Prognosis

Zhang²,

Zhang³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Background: The discovery that microRNAs (miRNAs) regulate proliferation, invasion and metastasis provides a principal molecular basis of tumor heterogeneity. Microvessel distribution is an important characteristic of solid tumors, with significant hypoxia occurring in the center of tumors with low blood flow. The distribution of miR-374a in breast tumors was examined as a factor likely to be important in breast cancer progression. Methods: Breast tissue samples from 40 patients with breast cancer were classified into two groups: a highly invasive and metastatic group (HIMG) and a low-invasive and metastatic Group (LIMG). Samples were collected from the center and edge of each tumor. In each group, six specimens were examined by microRNA array, and the remaining 14 specimens were used for real-time RT-qPCR, Western blot and immunohistochemical analyses. Correlation analysis was performed for the miRNAs and target proteins. Follow-up was carried out during 28 months to 68 months after surgery, and survival data were analyzed. Results: In the LIMG, the relative content of miR-374a was lower in the center of the tumor than at its edge; in the HIMG, it was lower at the edge of the tumor, and miR-374a levels were lower in breast cancer tissues than in normal tissues. There was no difference between VEGF-A and VCAM-1 mRNA levels at the edge and center of the tumor; however, we observed a significant difference between VEGF-A and VCAM-1 protein expression levels in these two regions. There was a negative correlation between miR-374a and target protein levels. The microvessel density (MVD) was lower in the center of the tumor than at its edge in HIMG, but the LIMG vessels were uniformly distributed. There was a significant positive correlation between MVD and the number of lymph node metastases (Pearson correlation, r=0.912, P<0.01). The median follow-up time was 48.5 months. LIMG had higher rate of disease-free survival (100%, P=0.013) and longer median survival time (66 months) than HIMG, which had a lower rate of 75% and shorter median survival time (54 months). Conclusions: Our data demonstrated miR-374a to be differentially distributed in breast cancer; VEGF-A and VCAM-1 mRNA had coincident distribution, and the distribution of teh respective proteins was uneven and opposite to that for the miR-374a. These data might explain the differences in the distribution of MVD in breast cancer and variation in breast cancer prognosis.

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Section: Discussionmentioning

confidence: 99%

Effects of Differential Distribution of Microvessel Density, Possibly Regulated by miR-374a, on Breast Cancer Prognosis

Zhang²,

Zhang³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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“…Studies have shown that the growth and progression of lymphomas are mediated by two mechanisms: autocrine stimulation of tumor cells via the expression of VEGF and its receptors by neoplastic cells, and the paracrine effect of a pro-angiogenic tumor microenvironment (CAO et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…Thus, it is believed that VEGF may act in tumorigenesis, regardless of angiogenesis and lymphangiogenesis (SENGER, 2010; PERROT-APPLANAT; DI BENEDETTO, 2012;CAO et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Serum concentration and immunostaining of vascular endothelial growth factor in dogs with multicentric lymphoma

Rodigheri

Calazans

Amorim³

et al. 2015

Sem. Ci. Agr.

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Vascular endothelium growth factor (VEGF) is one of the most specific regulators of tumor angiogenesis and lymphangiogenesis. Moreover, VEGF plays a role in tumorigenesis through activation of an autocrine signaling pathway that enables cancer cells to stimulate their own growth. The aim of this study was to investigate VEGF serum levels and immunoexpression in canine multicentric lymphomas and correlate these parameters with the prognostic factors of this cancer. Sixteen dogs were evaluated (eight clinically healthy and eight diagnosed with multicentric lymphoma). The animals underwent blood sampling to measure VEGF serum concentrations and lymph node biopsy to evaluate VEGF immunoexpression. The VEGF immunoreactivity score was higher (p=0.0003) in the lymph nodes of dogs with multicentric lymphoma (8.50±2.33) than in those of healthy dogs (1.87±1.80). There was no significant difference in the VEGF serum concentrations between healthy dogs and dogs with lymphoma (p=0.08). Immunophenotype, clinical stage and grade of malignancy influenced the life expectancy of dogs with lymphoma. Our results showed that VEGF is expressed in high amounts in the lymph nodes of dogs with multicentric lymphoma and may be responsible for the growth, survival and migration of tumor cells.

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“…Previously, neuropilin-1 (NRP-1, NP-1) a semaphorine receptor involved in axon guidance during brain development [34,35] has been shown to play a role in angiogenesis-independent malignant progression [36] by increasing the affinity of various VEGF ligands to the primary VEGF-receptors. Cariboni et al were also able to illustrate a KDR and blood vessel independent way via VEGF-NRP-1 interactions [37].…”

Section: Identification Of Key Angiogenic Factorsmentioning

confidence: 99%

Brain Tumor–Induced Angiogenesis: Approaches and Bioassays

Hock¹,

Fan²,

Buchfelder³

et al. 2013

Evolution of the Molecular Biology of Brain Tumors and the Therapeutic Implications

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VEGF Exerts an Angiogenesis-Independent Function in Cancer Cells to Promote Their Malignant Progression

Cited by 119 publications

References 19 publications

Effects of Differential Distribution of Microvessel Density, Possibly Regulated by miR-374a, on Breast Cancer Prognosis

Effects of Differential Distribution of Microvessel Density, Possibly Regulated by miR-374a, on Breast Cancer Prognosis

Serum concentration and immunostaining of vascular endothelial growth factor in dogs with multicentric lymphoma

Brain Tumor–Induced Angiogenesis: Approaches and Bioassays

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