Insulin-like growth factor receptor I (IGF-IR) and vascular endothelial growth factor receptor 2 (VEGFR-2) are expressed on the circulating epithelial tumor cells of breast cancer patients.

Monika Pizon,Katharina Pachmann,Ulrich Pachmann,Dorothea Sonja Zimon,Mohammad O Hoque

doi:10.1371/journal.pone.0056836

Abstract

BackgroundCirculating epithelial tumor cell (CETC) analysis is a promising diagnostic field for estimating the risk for metastatic relapse and progression in patients with malignant disease. CETCs characterization can be used as a liquid biopsy for prognostic and predictive purposes in breast and other cancers. IGF-IR and VEGFR-2 play an important role in tumor growth and the progression of cancer disease. The purpose of the current study was therefore to investigate their expression on CETCs.MethodsCETCs were determined from the blood of 50 patients suffering from breast cancer. The number of vital CETCs and the expression of IGF-IR and VEGFR-2 were investigated using the maintrac® method.ResultsIGF-IR and VEGFR-2 expression on the surface of CETCs were detected in 84% of patients. A statistically high correlation was found between IGF-IR and VEGFR-2 (r = 0.745 and p<0.001) on the CETCs. The co-expression of both receptors was confirmed in some experiments and ranged between 70% and 100%. Statistically significant correlations were observed between the number of CETCs and IGF-IR (r = 0.315 and p<0.05) and VEGFR-2 (r = 0.310 and p<0.05) expression. The presence of CETCs and the level of IGF-IR and VEGFR-2 expression were not associated with tumor stage, hormone receptor status or nodal/distant metastasis.SummaryIn this study, a parallel and co-expression of IGF-IR and VEGFR-2 was examined on the surface of CETCs in breast cancer patients for the first time. Characterization of CETCs may be a promising approach for the rational design of targeted anticancer therapies.

Highlights

Breast cancer is one of the most common cancers among women in the Western world
MCF-7 cell line was used as positive control for EpCAM expression and as negative control for IGF-IR and Vascular Endothelial Growth Factor Receptor 2 (VEGFR-2) staining of the Circulating epithelial tumor cell (CETC) (Figure 2)
No statistically significant differences in CETC numbers were observed according to tumor size, lymph node status, presence of metastasis or clinical pathology (p.0.05) (Table 1)

Summary

Introduction

Breast cancer is one of the most common cancers among women in the Western world. Despite improvements in early diagnosis and clinical management, breast cancer kills more than 520,000 people worldwide each year. IGF-IR and VEGFR-2, have been shown to play an important role in the growth of the primary tumor and metastasis formation. IGF-IR belongs to the family of transmembrane receptor tyrosine kinases and is expressed on the cell surface of most tissues. This receptor and its ligands play a key role in the regulation of growth and metabolism. We have used the maintracH approach [13], to determine the expression of IGF-IR and VEGFR-2 on CETCs in the peripheral blood of patients with breast cancer. IGF-IR and VEGFR-2 play an important role in tumor growth and the progression of cancer disease. The purpose of the current study was to investigate their expression on CETCs

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