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

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.

Expression of insulin‐like growth factor‐1 receptor in circulating tumor cells of patients with breast cancer is associated with patient outcomes

“…Insulin-like growth factor-1 receptor-expressing CTCs were detected in the majority of patients with early or metastatic breast cancer. Similarly, de Bono et al (2007) also showed that IGF1R is frequently expressed in CTCs of patients with metastatic tumors, whereas Pizon et al (2013) reported that 84% of patients with breast cancer had IGF1R-expressing CTCs. Interestingly, here we report that IGF1R immunostaining is more frequently observed among CTCs in early compared to metastatic disease.…”

“…() also showed that IGF1R is frequently expressed in CTCs of patients with metastatic tumors, whereas Pizon et al . () reported that 84% of patients with breast cancer had IGF1R‐expressing CTCs. Interestingly, here we report that IGF1R immunostaining is more frequently observed among CTCs in early compared to metastatic disease.…”

Granzyme B‐truncated VEGF fusion protein represses angiogenesis and tumor growth of OSCC

“…VEGFRs are the most important molecular targets for tumor therapy. VEGFR‐1 and VEGFR‐2 are overexpressed not only in endothelial cells, but also in many kinds of non‐endothelial tumor cells (Bairey et al , ; Spannuth et al , ; Pizon et al , ). It has been reported that VEGFRs overexpression are detected in most clinic human OSCC specimens (Ariotti et al , ; Pianka et al , ).…”

Novel human Ab against vascular endothelial growth factor receptor 2 shows therapeutic potential for leukemia and prostate cancer

“…The Pathology Atlas database indicates that VEGFR2 protein can be detected by immunohistochemical staining with verified Abs in cancer cells of 10%‐40% of surgical tumor sections, including urothelial, prostate, head and neck, cervical, and skin cancer . Interestingly, circulating tumor cells in the blood of breast cancer and small‐cell lung cancer patients were also found to express VEGFR2, and such expression is associated with tumor metastasis and poor prognosis . Therefore, blocking VEGFR2‐mediated signaling in both tumor endothelial and malignant cells is considered to be a promising strategy for new cancer treatments …”