Figure S3 from Growth of Triple-Negative Breast Cancer Cells Relies upon Coordinate Autocrine Expression of the Proinflammatory Cytokines IL-6 and IL-8

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

doi:10.1158/0008-5472.22397978.v1

Figure S3 from Growth of Triple-Negative Breast Cancer Cells Relies upon Coordinate Autocrine Expression of the Proinflammatory Cytokines IL-6 and IL-8

journal contribution

posted on 2023-03-30, 21:53 authored by 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

Figure S3 - PDF file 1318K, Expression LPAR2 in breast cancers, and the importance of LPAR2 in the expression of cytokines in SUM159

History

ARTICLE 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. Cancer Res; 73(11); 3470–80. ©2013 AACR.