Breast tumors induce the recruitment of AC133+KDR+ endothelial precursor cells mobilized by plasma vascular endothelial growth factor

M Botelho,I Amendoeira,J Diamond,F Schmitt,S Dias

doi:10.1186/bcr1187

Abstract

Recent evidence has demonstrated the importance of bone marrow-derived endothelial precursor cells (EPC) in the contribution to postnatal physiological and pathological neovascularization, and in tumor growth and angiogenesis. These cells are recruited undifferentiated; in response to systemic or chemoattractive signals, such as vascular endothelial growth factor (VEGF), they lodge in the growing or lesioned tissue and differentiate into endothelial cells in response to local stimuli and cell–cell interactions. The extent and the significance of the EPC contribution for the growing of most tumors, including breast carcinomas, are still not defined. We analysed the peripheral blood mononuclear cells (PBMNC) of 48 breast cancer patients and found that 16.7% of them have circulating EPC. These cells were detected by RT-PCR expression of AC133 and kinase domain receptor (KDR). Furthermore, using an ELISA assay, we also found an association between circulating AC133+KDR+ cells and VEGF plasma levels in these patients. We also found AC133 and KDR positivity in breast carcinoma tissues. To our knowledge, this is the first report addressing the recruitment of EPC to breast tumors. Strategies to impair the mobilization and incorporation of EPC into tumors may interfere with the growth of these tumors.

Highlights

Endocrine therapy for breast cancer is a major modality for the treatment of breast cancer, producing response rates between 30% and 40% of unselected patients with the minimum of toxicity
We have shown that overexpression of TGF-β1 in mammary epithelial cells suppresses the development of carcinomas and that expression of a dominant negative type II TGF-β receptor (DNIIR) in mammary epithelial cells under control of the MMTV promoter/enhancer increases the incidence of erbB2 in carcinomas accompanied by Tgfbr2fspKO fibroblasts
The present article reviews results from neoadjuvant studies in which endocrine therapy was given to patients whose primary breast cancer was still within the breast so that changes in tumour volume could be used to assess clinical response and so that sequential biopsies could be taken for molecular analyses designed to identify predictive markers

Summary

Introduction

Endocrine therapy for breast cancer is a major modality for the treatment of breast cancer, producing response rates between 30% and 40% of unselected patients with the minimum of toxicity. Several human genetic diseases are known to be or suspected to be due to defects in DNA repair or cell cycle control Some of these patients are radiation sensitive and/or predisposed for cancer as a cause of mutations in genes involved in these cellular pathways. Microarray-based comparative genomic hybridization (arrayCGH) allows the construction of high-resolution genome-wide maps of copy number alterations, and statistical software packages are available for exploring and analysing array-CGH data (see, for example, [2,3]), facilitating the delineation of the boundaries of CNAs in individual tumors and thereby localizing and identifying potential oncogenes and tumor suppressor genes. The aim of this study was to evaluate the prognostic value of gene expression-based classification as well as established prognostic markers, including mutation status of the TP53 gene, in a group of breast cancer patients with long-term (>10 years) fol The aim of this study was to compare MR spectroscopic findings from breast cancer tissue with histological grading of tumor and patient lymph node status

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