NILCO biomarkers in breast cancer from Chinese patients

• Type of Material: Article
• Authors: Laronna S Colbert, Morehouse School of Medicine; Kaamilah Wilson, Morehouse School of Medicine; Sungjin Kim, Emory University; Yuan Liu, Emory University; Gabriela M Oprea, Emory University; Corey Gillespie, Morehouse School of Medicine; Toi Dickson, Morehouse School of Medicine; Gale Newman, Morehouse School of Medicine; Ruben Rene Gonzalez-Perez, Morehouse School of Medicine
• Language: English
• Date: 2014
• Publisher: BioMed Central
• Publication Version: Final Published Version
• Copyright Statement: © 2014 Colbert et al.; licensee BioMed Central Ltd.
• License: Creative Commons Attribution 2.0 Generic
• Final Published Version (URL): http://www.biomedcentral.com/1471-2407/14/249
• Title of Journal or Parent Work: BMC Cancer
• Volume: 14
• Issue: 249
• Grant/Funding Information: This work was partially supported by the National Institutes of Health and National Cancer Institute Grant 1SC1CA138658-05 and U54 CA118638, the Georgia Cancer Coalition Distinguished Cancer Scholar Award, and DOD Idea Award BC 123427 to RRGP; a grant from CREDO (MSCR) 2R25RR017694-06A1 to LSC; the Blackstone Academy and NIH/NIDDK Step-up HS Research Program to K.W.; and facilities, and support services at Morehouse School of Medicine (NIH RR03034 and 1C06 RR18386) and NIH/NCRR grant 1G12RR026250-03.
• Research Categories: Health Sciences, Oncology; Health Sciences, Public Health

Abstract

Background Notch, IL-1 and leptin are known pro-angiogenic factors linked to breast cancer development, tumor aggressiveness and poor prognosis. A complex crosstalk between these molecules (NILCO) has been reported in breast cancer cell lines. However, whether NILCO biomarkers are differentially expressed in estrogen responsive (ER+), unresponsive (ER-) and triple negative (TNBC) breast cancer tissues is unknown. Methods Expression levels of nine NILCO and targets [Notch1, Notch4, JAG1, DLL4, VEGF, VEGFR2 (FLK-1), leptin, leptin receptor (OB-R) and interleukin-1 receptor type I (IL-1R tI)] were examined via immunohistochemistry in breast cancer tissue microarrays from Chinese patients (ER+, n=33; ER-, n=21; TNBC, n=13) and non-malignant breast tissue (n=5; Pantomics, Inc.) using a semi-quantitative analysis of intensity staining, HSCORE. Results Categorical expression of NILCO and targets (+ or -) was similar among all cancer tissues. However, TNBC showed differential localization pattern of NILCO. TNBC showed fewer nuclei and cytoplasms positive for Notch4 and JAG1, but more cytoplasms positive for leptin. In addition, fewer TNBC stromas were positive for Notch1 and Notch4, but 100% of TNBC stromas were positive for VEGFR2. Moreover, TNBC had lower DLL4 and IL-1R tI expression. TNBC and ER- showed higher expression of EGFR, but lower expression of AR. Leptin and OB-R were detected in more than 61% of samples. Leptin positively correlated to OB-R, JAG1, VEGF, and marginally to IL-1R tI. Notch1 positively correlated to IL-1R tI. EGFR and Ki67 were positively associated to Notch1, but no associations of NILCO and targets with p53 were found. Conclusions Present data suggest that NILCO components are differentially expressed in breast cancer. TNBC showed distinctive patterns for NILCO expression and localization. The complex crosstalk between leptin, IL-1 and Notch could differentially drive breast cancer growth and angiogenesis. Furthermore, the analysis of NILCO and targets using Pathway Studio9 software (Ariadine Genomics) showed multiple molecular relationships that suggest NILCO has potential prognostic biomarker value in breast cancer.