Significance of vascular endothelial growth factor (VEGF)/soluble VEGF receptor‐1 relationship in breast cancer

Abstract

Angiogenesis, the formation of new blood vessels, is controlled by a balance between positive and negative endothelial regulatory factors. Soluble vascular endothelial growth factor receptor-1 (sVEGFR1), a naturally occurring soluble form of VEGFR1, is a negative counterpart of the vascular endothelial growth factor (VEGF) signaling pathway, which has been characterized as one of the most important endothelial regulators in human tumor angiogenesis. In our study, we examined the expression of sVEGFR1 in 110 primary breast carcinomas, and assessed its clinical significance. Ninety-four of 110 tumors showed >0.1 ng/mg protein of sVEGFR1 (range: 0.1-6.9 ng/mg protein; median: 1.03 ng/mg protein) as determined by a specific enzyme-linked immunosorbent assay (ELISA). Immunoblot analysis confirmed the presence of sVEGFR1 in breast tumor tissues. The levels of sVEGFR1 were correlated significantly with the levels of VEGF. There was no significant correlation between the levels of sVEGFR1 and any clinico-pathological factors including age, menopause, nodal involvement and hormone receptor status. A univariate prognosis analysis showed that the intratumoral VEGF status, as determined by ELISA, was a significant prognostic indicator, but sVEGFR1 status was not. In the combined analysis, however, the ratio of sVEGFR1 and VEGF levels provided more statistically significant prognostic value than VEGF status alone. Tumors in which the sVEGFR1 levels exceeded VEGF levels 10-fold had a markedly favorable prognosis. Multivariate analysis also demonstrated that the ratio of sVEGFR1 and VEGF was an independent prognostic indicator after nodal status. In conclusion, sVEGFR1, an intrinsic inhibitor of VEGF, frequently co-expressed with VEGF in primary breast cancer tissues. The intratumoral balance between sVEGFR1 and VEGF levels might be crucial for the progression of breast cancer.

Protein expression profiling of vascular endothelial growth factor and its receptors identifies subclasses of hepatocellular carcinoma and predicts survival

“…VEGF-A and VEGF-C are the major factors in the progression and metastasis of many malignancies as well as the important risk factors for prognosis (Otrock et al 2007;Hicklin and Ellis 2005;Toi et al 2002); however, there were few reported studies about the prognosis signiWcance of VEGF receptors in tumor or the peritumoral area. We used an unsupervised hierarchical clustering analysis to classify the 107 HCC patients into meaningful prognostic groups based on the minimal set of biomarkers of VEGF/ VEGFR.…”

Impact of type 2 diabetes on the plasma levels of vascular endothelial growth factor and its soluble receptors type 1 and type 2 in patients with peripheral arterial disease

“…This parameter could be used in practice to assess the degree of severity of PAD, which is the subject of the current research (Rość et al, 2014). The studies by Toi et al (2002) involving patients with breast cancer and the studies by Yamaguchi et al (2007) concerning individuals suffering from colorectal carcinoma, were focused on analyzing the sVEGFR-1/VEGF ratio in terms of clinical parameters and prognosis of cancer. This study showed stronger angiogenic inhibition capacity demonstrated by the ratio of concentrations (sVEGFR-1/ VEGF-A and sVEGFR-2/VEGF-A) in the control group in comparison with PAD subgroups.…”

Vascular Endothelial Growth Factor Mediates Intracrine Survival in Human Breast Carcinoma Cells through Internally Expressed VEGFR1/FLT1

“…However, this concept has now been challenged by recent reports showing that some cancer cells express VEGF receptors on their surfaces in vitro and in vivo, and that in several tumor cell types, including leukemia and melanoma cells, VEGF acts as an autocrine survival factor [22,23]. Although breast cancer cell lines express both VEGF and the VEGF receptors VEGFR1, VEGFR2, and NRP1 [11], the expression of these receptors in primary breast tumors is controversial [12,13,24–28]. Dales et al [12] reported that VEGFR1 and VEGFR2 were strongly expressed in endothelial cells within blood microvessels, and weakly expressed in tumor cells in a series of 918 patients.…”