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

Zachary C. Hartman, Graham M. Poage, Petra Den Hollander, Anna Tsimelzon, Jamal Hill, Nattapon Panupinthu, Yun Zhang, Abhijit Mazumdar, Susan G. Hilsenbeck, Gordon B. Mills, Powel H. Brown

Research output: Contribution to journalArticlepeer-review

237 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3470-3480
Number of pages11
JournalCancer Research
Volume73
Issue number11
DOIs
StatePublished - Jun 1 2013
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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