Abstract 5642: Wound-healing drainages contribute to triple negative breast cancers aggressiveness

Abstract

Abstract The triple negative breast cancers (TNBC) is an extremely aggressive cancer subtype that although account for only 10-17% of breast cancers carries the higher rate of distant recurrence and death than women with other breast cancer subtypes and, unfortunately has limited treatment options. The TNBC pattern of recurrence present a distant recurrence peak at approximately 3 years and then declines rapidly thereafter. It's now well known that growth-factors released during the healing process can accelerate the early recurrences in breast cancer patients. We speculate that wound healing drainages (WHD) stimulation may specifically contribute to TNBC early relapse. To this aim, a panel of TNBC cell lines (BT-549; HCC1937, MDA-MB-157; MDA-MB-231; MDA-MB-468; SUM159; SUM149) and the luminal cell lines MCF7 were treated with WHD. All breast carcinoma cell lines are induced to proliferate in response to more than 20 drainage fluids obtained from breast cancer patients, but median proliferation level was 3-folds higher in TNBC- compared to luminal-cell line. To identify which receptors/pathways can be activated and play a driving role in TNBC progression, a reverse phase protein microarray (RPMA) experiment on TNBC cells WHD stimulated was performed. We revealed a specific activation of PDGFR, VEGFR and their downstream pathways, whereas no significant changes were observed in other receptors, such as EGFR, IRS, Met and ERB3. Conversely, PDGFR and VEGFR pathways were not activated in MCF7. The type of activated receptors suggested the involvement of angiogenic properties, besides canonical proliferation pathways, upon WHD stimulation. To prove whether the receptors found activated by WHD play a key role in in vitro and in vivo TNBC progression, we targeted PDGFR, VEGFR and other receptors possibly involved in proliferation and angiogenic capabilities with sunitinib (targeting PDGFR, VEGFR, FGF and c-kit), anti-bFGF antibody (targeting the ligand bFGF) and bevacizumab (targeting the VEGF) in TNBC cells WHD-stimulated. Sunitinib and anti-bFGF antibody halved the proliferation of TNBC cell lines, whereas bevacizumab modestly affect proliferation. Notably, sunitinib and anti-bFGF antibody strongly inhibited MDA-MB-231 and MDA-MB-468 xenografts tumor growth (sunitinib: 80%, and 70% Growth Index (GI), respectively; anti-bFGF antibody 70% and 60% GI, respectively) whereas bevacizumab determined no more than 30% decrease of tumor volume. In conclusion, WHD promotes TNBC progression probably by sustaining both proliferation and angiogenic. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5642. doi:1538-7445.AM2012-5642