Abstract #LB-280: Expression of early placenta insulin-like growth factor in breast cancer a prerequisite of metastasis forming disseminated tumor cells?

EPIL is expressed physiologically in the so-called invasive phase of placenta development during first trimester of pregnancy. Differential gene expression analysis between breast cancer cell subclones (SKBR3) with and without transendothelial invasive revealed EPIL as an autocrine regulator of cell motility and proliferation. Such experimental data has been translated to a clinical setting by using a prognostic tissue microarray (p < 0.01; n=1400). Survival data analysis found a significant association between expression levels of EPIL and 5-year overall survival (OS) that was dose-dependent. Subsequently established cell lines with EPIL overexpression showed increased resistance to apoptosis and a 15-fold overexpression of the hematogeneous stem cell transcription factor GATA2. Stimulation of breast cancer cells in vitro by synthetic EPIL also led to GATA2 upregulation which was inverted by EPIL siRNA administration. Furthermore, EPIL and GATA 2 were detected simultaneously in breast cancers with a positive bone marrow status for disseminated tumor cells (DTC) by immunohistochemistry. Leftventricular application of EPIL-overexpressing breast cancer cells in immuno-deficient mice brought about bone marrow dissemination detected by RT-PCR. This is in agreement with the detection of EPIL in the tumors of breast cancer patients who harboured DTC in their bone marrow and formed metastasis whereas EPIL negative did not (p < 0.01). The results suggest that EPIL might be a cancer cell-produced growth factor that provides autocrine signaling for invasion, motility and survival, especially in the bone marrow.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr LB-280.