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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Hartman, ZC; Poage, GM; den Hollander, P; Tsimelzon, A; Hill, J; Panupinthu, N; Zhang, Y; Mazumdar, A; Hilsenbeck, SG; Mills, GB; Brown, PH

Published Date

  • June 2013

Published In

Volume / Issue

  • 73 / 11

Start / End Page

  • 3470 - 3480

PubMed ID

  • 23633491

Pubmed Central ID

  • 23633491

Electronic International Standard Serial Number (EISSN)

  • 1538-7445

International Standard Serial Number (ISSN)

  • 0008-5472

Digital Object Identifier (DOI)

  • 10.1158/0008-5472.CAN-12-4524-T

Language

  • eng