Non-Angiogenic Functions of VEGF in Breast Cancer

  title={Non-Angiogenic Functions of VEGF in Breast Cancer},
  author={Arthur M. Mercurio and Elizabeth A. Lipscomb and Robin E Bachelder},
  journal={Journal of Mammary Gland Biology and Neoplasia},
This review advances the hypothesis that the function of vascular endothelial growth factor (VEGF) in breast cancer is not limited to angiogenesis, and that VEGF signaling in breast carcinoma cells is important for the ability of these cells to evade apoptosis and progress towards invasive and metastatic disease. In other terms, VEGF signaling provides a selective advantage for the survival and dissemination of breast carcinoma cells that may be independent of angiogenesis. The key component of… 

Autocrine functions of VEGF in breast tumor cells

Vascular endothelial growth factor A (VEGF-A) is well known for its key roles in blood vessel growth. Although most studies on VEGF and VEGF receptors have been focused on their functions in

Overexpression of vascular endothelial growth factor 189 in breast cancer cells leads to delayed tumor uptake with dilated intratumoral vessels.

The data indicate that VEGF189 participates in mammary tumor growth through both angiogenesis and nonangiogenic functions, and in vitro results suggest an autocrine effect of V EGF189 on breast cancer cells, probably through neuropilin-1.

Molecular expression of vascular endothelial growth factor, prokineticin receptor-1 and other biomarkers in infiltrating canalicular carcinoma of the breast.

The aim of the present study was to assess the expression of VEGF, EG-VEGF and its receptor (prokineticin receptor-1), as well as that of breast cancer resistant protein, estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2, in 50 breast samples of infiltrating canalicular carcinoma (ICC) and their correlation with tumor staging.

VEGF signaling inhibitors: More pro-apoptotic than anti-angiogenic

  • R. Epstein
  • Biology
    Cancer and Metastasis Reviews
  • 2007
The emerging model of anti-VEGF drug action being mediated primarily by tumoral (as distinct from endothelial) VEGFRs has clinically important implications for optimizing the anti-metastatic efficacy of this expanding drug class.

Migration-promoting role of VEGF-C and VEGF-C binding receptors in human breast cancer cells

The novel role of tumour-derived VEGF-C indicates that breast cancer metastasis can be promoted by coordinated stimulation of lymphangiogenesis and enhanced migratory activity of breast cancer cells.

Overexpression of VEGF189 in breast cancer cells induces apoptosis via NRP1 under stress conditions

A major role of NRP1 in apoptosis induced by VEGF189 in stress conditions is suggested and confirmed as a survival factor for breast tumor cells.

How VEGF-A and its splice variants affect breast cancer development – clinical implications

It is demonstrated that cytoplasmatic VEGFA/165b expression is higher in invasive breast cancer tumor cells than in normal tissues or stroma and may be the starting point for further studies at a quantitative level, which can be a major step towards the design of targeted antibody-based (breast) cancer therapies.

Inhibition of the VEGF signaling pathway attenuates tumor-associated macrophage activity in liver cancer

It was observed that TAMs cultured in a VEGF-depleted environment displayed lower secretion levels of cytokines involved in tumor progression and a decreased immune tolerance-inducing ability, suggesting that VEGf inhibition in TAMs may be a potential therapeutic target for liver cancer.

Angiogenesis: bFGF and VEGF in breast carcinoma

A substantial body of experimental evidence supports the hypothesis that angiogenesis and angiogenic factors may be strong prognostic and predictive factors in breast carcinoma.

Anticancer effect of rapamycin on MCF-7 via downregulation of VEGF expression

The findings suggest that mTOR acts as a direct anticancer agent and that the mTOR-inhibitor-induced anticancer effect involved the reduced expression of VEGF in MCF-7.



Vascular endothelial growth factor (VEGF) is an autocrine growth factor for VEGF receptor-positive human tumors.

VEGF is an autocrine growth factor for tumor cell lines that express VEGFRs and it is shown that inhibition of VEGF (VEGF antisense oligonucleotide AS-3) or V EGFRs (neutralizing antibodies) inhibited the proliferation of these cell lines in vitro.

A potential role for vascular endothelial growth factor-D as an autocrine growth factor for human breast carcinoma cells.

Findings suggest that VEGF-D functions both as an autocrine growth factor and a stimulator of angiogenesis in breast cancer.

Vascular endothelial growth factor promotes breast carcinoma invasion in an autocrine manner by regulating the chemokine receptor CXCR4.

The findings indicate that a VEGF autocrine pathway induces chemokine receptor expression in breast carcinoma cells, thus promoting their directed migration toward specific chemokines.

Vascular endothelial growth factor is an autocrine survival factor for neuropilin-expressing breast carcinoma cells.

We identify a novel function for the vascular endothelial growth factor (VEGF) in its ability to stimulate an autocrine signaling pathway in metastatic breast carcinoma cells that is essential for

Vascular stroma formation in carcinoma in situ, invasive carcinoma, and metastatic carcinoma of the breast.

  • L. BrownA. Guidi H. Dvorak
  • Medicine, Biology
    Clinical cancer research : an official journal of the American Association for Cancer Research
  • 1999
It is concluded that a distinct pattern of mRNA expression characterizes the generation of vascularStroma in breast cancer and that the formation of vascular stroma may play a role not only in growth of the primary tumor but also in invasion and metastasis.

Vascular endothelial growth factor (VEGF) upregulates BCL-2 and inhibits apoptosis in human and murine mammary adenocarcinoma cells

VEGF resulted in reduced tumour cell apoptosis, whereas its inhibition with anti-VEGF neutralizing antibodies induced apoptosis directly in tumour cells, therefore, in addition to its role in angiogenesis and vessel permeability, VEGF acts as a survival factor for tumours, inducing Bcl-2 expression and inhibiting tumours apoptosis.

The biology of VEGF and its receptors

Vascular endothelial growth factor (VEGF) is a key regulator of physiological angiogenesis during embryogenesis, skeletal growth and reproductive functions. VEGF has also been implicated in

De novo expression of vascular endothelial growth factor in human pancreatic cancer: evidence for an autocrine mitogenic loop.

The results not only support the important role of the VEGF/VEGF receptor system in pancreatic tumor biology but also suggest the existence of an autocrine/paracrine mitogenic loop for pancreatic cancer cells.

Targeting autocrine and paracrine VEGF receptor pathways inhibits human lymphoma xenografts in vivo.

It is demonstrated here that human lymphoma cells secrete vascular endothelial growth factor (VEGF) and express VEGF receptor 1 (VEGFR-1) and VEGFR-2 and that combining DC101 with therapeutic agents consistently improved tumor responses over those of single-agent therapy.

VEGF contributes to mammary tumor growth in transgenic mice through paracrine and autocrine mechanisms

The data from these transgenic models indicate that VEGF contributes to mammary tumor growth through increased neovascularization, as well as autocrine stimulation of growth and inhibition of apoptosis.