Format

Send to

Choose Destination
Cancer Res. 2013 Jun 1;73(11):3470-80. doi: 10.1158/0008-5472.CAN-12-4524-T. Epub 2013 Apr 30.

Growth of triple-negative breast cancer cells relies upon coordinate autocrine expression of the proinflammatory cytokines IL-6 and IL-8.

Author information

1
Department of Clinical Cancer Prevention and Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Abstract

Triple-negative breast cancers (TNBC) are aggressive with no effective targeted therapies. A combined database analysis identified 32 inflammation-related genes differentially expressed in TNBCs and 10 proved critical for anchorage-independent growth. In TNBC cells, an LPA-LPAR2-EZH2 NF-κB signaling cascade was essential for expression of interleukin (IL)-6, IL-8, and CXCL1. Concurrent inhibition of IL-6 and IL-8 expression dramatically inhibited colony formation and cell survival in vitro and stanched tumor engraftment and growth in vivo. A Cox multivariable analysis of patient specimens revealed that IL-6 and IL-8 expression predicted patient survival times. Together these findings offer a rationale for dual inhibition of IL-6/IL-8 signaling as a therapeutic strategy to improve outcomes for patients with TNBCs.

PMID:
23633491
PMCID:
PMC3853111
DOI:
10.1158/0008-5472.CAN-12-4524-T
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center