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

doi:10.1158/0008-5472.CAN-12-4524-T

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

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321 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 language	English (US)
Pages (from-to)	3470-3480
Number of pages	11
Journal	Cancer Research
Volume	73
Issue number	11
DOIs	https://doi.org/10.1158/0008-5472.CAN-12-4524-T
State	Published - Jun 1 2013

ASJC Scopus subject areas

Oncology
Cancer Research

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Hartman, Z. C., Poage, G. M., Den Hollander, P., Tsimelzon, A., Hill, J., Panupinthu, N., Zhang, Y., Mazumdar, A., Hilsenbeck, S. G., Mills, G. B., & Brown, P. H. (2013). Growth of triple-negative breast cancer cells relies upon coordinate autocrine expression of the proinflammatory cytokines IL-6 and IL-8. Cancer Research, 73(11), 3470-3480. https://doi.org/10.1158/0008-5472.CAN-12-4524-T

Hartman, ZC, Poage, GM, Den Hollander, P, Tsimelzon, A, Hill, J, Panupinthu, N, Zhang, Y, Mazumdar, A, Hilsenbeck, SG, Mills, GB & Brown, PH 2013, 'Growth of triple-negative breast cancer cells relies upon coordinate autocrine expression of the proinflammatory cytokines IL-6 and IL-8', Cancer Research, vol. 73, no. 11, pp. 3470-3480. https://doi.org/10.1158/0008-5472.CAN-12-4524-T

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

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.",

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AU - Hartman, Zachary C.

AU - Poage, Graham M.

AU - Den Hollander, Petra

AU - Tsimelzon, Anna

AU - Hill, Jamal

AU - Panupinthu, Nattapon

AU - Zhang, Yun

AU - Mazumdar, Abhijit

AU - Hilsenbeck, Susan G.

AU - Mills, Gordon B.

AU - Brown, Powel H.

PY - 2013/6/1

Y1 - 2013/6/1

N2 - 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.

AB - 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.

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

Abstract

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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