Growth of triple-negative breast cancer cells relies upon coordinate autocrine expression of the proinflammatory cytokines IL-6 and IL-8
ZC Hartman, GM Poage, P Den Hollander, A Tsimelzon… - Cancer research, 2013 - AACR
Cancer research, 2013•AACR
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 …
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 …
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.
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