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

Toi, Masakazu; Bando, Hiroko; Ogawa, Taeko; Muta, Mariko; Hornig, Carsten; Weich, Herbert A.

doi:10.1002/ijc.10121.abs

Cited by 34 publications

(49 citation statements)

References 4 publications

(4 reference statements)

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“…The current study using a highly sensitive sVEGFR-1 ELISA system confirmed that sVEGFR-1 is a significant prognostic indicator. In particular, we discovered that low sVEGFR-1 was related to an unfavourable prognosis, which was a slightly different result from that we had in a previous study with a relatively low-sensitivity sVEGFR-1 ELISA system, where we found a prognostic value of high sVEGFR-1 concentrations for favourable prognosis (Toi et al, 2002). The significance of the ratio of sVEGFR-1 to total VEGF (S/V ratio) as a prognostic marker was reconfirmed in this larger size of analysis.…”

Section: Discussioncontrasting

confidence: 94%

“…Kendall et al (1996) found that sVEGFR1 is abundant in all identified VEGFR-1 cDNAs from human primary endothelial cells. In our preliminary study using primary breast cancer tissues, sVEGFR1 was frequently coexpressed with VEGF, and the intratumoral balance between sVEGFR1 and VEGF levels showed a significant relationship with survival (Toi et al, 2002). According to a recent report on brain tumours, the ratio of sVEGFR-1 to VEGF is significantly decreased in glioblastomas compared with astrocytomas, which indicates the importance of sVEGFR-1 expression in brain tumour growth (Lamszus et al, 2003).…”

mentioning

confidence: 78%

“…Enzyme-linked immunosorbent assay for sVEGFR-1 was performed as previously reported with modifications to improve sensitivity (Toi et al, 2002). A human sVEGFR-1 ELISA kit (Bender MedSystems, Vienna, Austria) was used according to the manufacturer's protocol.…”

Section: Enzyme-linked Immunosorbent Assaymentioning

confidence: 99%

“…To assess the prognostic value of sVEGFR-1 and the ratio of sVEGFR-1 to total VEGF, we determined the cutoff level according to a stepwise method that gives the optimal separation between a low and high risk of relapse as previously described (Toi et al, 2002). The cutoff value for sVEGFR-1 was 0.435 ng mg À1 protein, which identified 15.6% of the patients enrolled in the survival analysis as having low sVEGFR-1.…”

Section: Patient Characteristicsmentioning

confidence: 99%

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Association between intratumoral free and total VEGF, soluble VEGFR-1, VEGFR-2 and prognosis in breast cancer

et al. 2005

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Vascular endothelial growth factor (VEGF) receptors consist of three cell-membrane type receptors (VEGFR-1, VEGFR-2 and VEGFR-3), and soluble form of VEGFR-1 (sVEGFR-1), an intrinsic negative counterpart of the VEGF. In this study, we measured intratumoral protein levels of free and total VEGF, VEGFR-2 and sVEGFR-1 from 202 primary breast cancer tissues and examined their prognostic values. A significant inverse correlation was found between free or total VEGF and oestrogen receptor (ER) status ( P =0.042 and 0.032, respectively). A univariate analysis showed that low sVEGFR-1 and high total VEGF were significantly associated with poor prognosis in disease-free survival (DFS) and overall survival (OS). The ratio of sVEGFR-1 to total VEGF was a strong prognostic indicator (DFS: P =0.008; OS: P =0.0002). A multivariate analysis confirmed the independent prognostic values of total VEGF and the ratio of sVEGFR-1 to total VEGF. In subgroup analysis, total VEGF was a significant prognostic indicator for ER-positive tumours but not for ER-negative tumours, whereas sVEGFR-1 was significant for ER-negative tumours but not for ER-positive tumours. In conclusion, the intratumoral sVEGFR-1 level, VEGF level and the ratio of sVEGFR-1 to total VEGF are potent prognostic indicators of primary breast cancer, and might be relevant to ER status.

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Section: Discussioncontrasting

confidence: 94%

mentioning

confidence: 78%

Section: Enzyme-linked Immunosorbent Assaymentioning

confidence: 99%

Section: Patient Characteristicsmentioning

confidence: 99%

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Association between intratumoral free and total VEGF, soluble VEGFR-1, VEGFR-2 and prognosis in breast cancer

et al. 2005

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“…14 The VEGFR-1 sandwich immunoassay used 1 monoclonal anti-human VEGFR-1 antibody and 1 polyclonal antibody. 22,23 …”

Section: Measurement Of Total-vegf-a Free-vegf-a Vegf-c and Vegfr-1mentioning

confidence: 99%

Immunodetection and quantification of vascular endothelial growth factor receptor‐3 in human malignant tumor tissues

Bando

Brokelmann

Toi

et al. 2004

Intl Journal of Cancer

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Vascular endothelial growth factor recpetor-3 (VEGFR-3) and its ligands, vascular endothelial growth factor-C (VEGF-C) and -D (VEGF-D), are the major molecules involved in developmental and pathological lymphangiogenesis. Here we describe for the first time the development of a specific indirect enzyme-linked immunosorbent assay (ELISA) for the quantification of VEGFR-3 in different human cell and tissue lysates. A combination of the goat polyclonal anti-VEGFR-3 antibody and the mouse monoclonal anti-human VEGFR-3 antibody was used. The assay was highly sensitive and reproducible with a detection range of 0.2-25 ng/ ml. The assay was specific for VEGFR-3, with no crossreactivity to VEGFR-1 or VEGFR-2. Complex formation with VEGF-C and VEGF-D had no effect on the sensitivity of the assay. The VEGFR-3 concentration in the lysates of cultured human dermal microvascular endothelial cells was 14-fold higher than in the lysates from human umbilical vein endothelial cells. In human kidney, breast, colon, gastric and lung cancer tissues the protein levels of VEGFR-3 were in the range of 0.6 -16.7 ng/mg protein. Importantly, the level of VEGFR-3 protein detected in the ELISA correlated significantly with the number of VEGFR-3 positive vessels observed in histochemical sections, suggesting that the ELISA assay may be a reliable surrogate of measuring VEGFR-3-positive vessel density. The protein levels of VEGFR-3 in 27 renal cell carcinoma samples had a significant correlation with the levels of VEGF-C (p<0.001), or biological active, free VEGF-A (p<0.0001), but not with VEGFR-1 or total VEGF-A. This assay provides a useful tool for the investigations of the expression levels of VEGFR-3 in physiological and pathological processes, particular in cancer and in lymphangiogenesisrelated disease.

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Monitoring multiple angiogenesis‐related molecules in the blood of cancer patients shows a correlation between VEGF‐A and MMP‐9 levels before treatment and divergent changes after surgical vs. conservative therapy

Zaman

Driscoll

Hahn

et al. 2005

Intl Journal of Cancer

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Anti-angiogenic therapies are currently in cancer clinical trials, but to date there are no established tests for evaluating the angiogenic status of a patient. We measured 11 circulating angiogenesis-associated molecules in cancer patients before and after local treatment. The purpose of our study was to screen for possible relationships among the different molecules and between individual molecules and tumor burden. We measured VEGF-A, PlGF, SCF, MMP-9, EDB 1 -fibronectin, sVEGFR-2, sVEGFR-1, saVb3, sTie-2, IL-8 and CRP in the blood of 22 healthy volunteers, 17 early breast, 17 early colorectal, and 8 advanced sarcoma/melanoma cancer patients. Breast cancer patients had elevated levels of VEGF-A and sTie-2, colorectal cancer patients of VEGF-A, MMP-9, sTie-2, IL-8 and CRP, and melanoma/sarcoma patients of sVEGFR-1. saVb3 was decreased in colorectal cancer patients. A correlation between VEGF-A and MMP-9 was found. After tumor removal, MMP-9 and saVb3 significantly decreased in breast and CRP in colorectal cancer, whereas sVEGFR-1 increased in colorectal cancer patients. In sarcoma/melanoma patients treated regionally with TNF and chemotherapy we observed a rise in VEGF-A, SCF, VEGFR-2, MMP-9, Tie-2 and CRP, a correlation between CRP and IL-8, and a decreased in sVEGFR-1 levels. In conclusion, among all factors measured, only VEGF-A and MMP-9 consistently correlated to each other, elevated CRP levels were associated with tumor burden, whereas sVEGF-R1 increased after tumor removal in colorectal cancer. Treatment with chemotherapy and TNF induced changes consistent with an angiogenic switch. These results warrant a prospective study to compare the effect of surgical tumor removal vs. chemotherapy on some of these markers and to evaluate their prognostic/predictive value. ' 2005 Wiley-Liss, Inc.Key words: surrogate markers; angiogenesis; predictive; TNF; chemotherapy Angiogenesis promotes local tumor progression and invasion and enables tumor cell dissemination and metastasis formation.

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

Cited by 34 publications

References 4 publications

Association between intratumoral free and total VEGF, soluble VEGFR-1, VEGFR-2 and prognosis in breast cancer

Association between intratumoral free and total VEGF, soluble VEGFR-1, VEGFR-2 and prognosis in breast cancer

Immunodetection and quantification of vascular endothelial growth factor receptor‐3 in human malignant tumor tissues

Monitoring multiple angiogenesis‐related molecules in the blood of cancer patients shows a correlation between VEGF‐A and MMP‐9 levels before treatment and divergent changes after surgical vs. conservative therapy

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