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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.

Publication ,  Journal Article
Hartman, ZC; Poage, GM; den Hollander, P; Tsimelzon, A; Hill, J; Panupinthu, N; Zhang, Y; Mazumdar, A; Hilsenbeck, SG; Mills, GB; Brown, PH
Published in: Cancer Res
June 1, 2013

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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Published In

Cancer Res

DOI

EISSN

1538-7445

Publication Date

June 1, 2013

Volume

73

Issue

11

Start / End Page

3470 / 3480

Location

United States

Related Subject Headings

  • Triple Negative Breast Neoplasms
  • Transfection
  • Signal Transduction
  • Proportional Hazards Models
  • Oncology & Carcinogenesis
  • Neoplastic Stem Cells
  • Mice, Nude
  • Mice
  • Interleukin-8
  • Interleukin-6
 

Citation

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Hartman, Z. C., Poage, G. M., den Hollander, P., Tsimelzon, A., Hill, J., Panupinthu, N., … 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 Res, 73(11), 3470–3480. https://doi.org/10.1158/0008-5472.CAN-12-4524-T
Hartman, Zachary C., Graham M. Poage, Petra den Hollander, Anna Tsimelzon, Jamal Hill, Nattapon Panupinthu, Yun Zhang, et al. “Growth of triple-negative breast cancer cells relies upon coordinate autocrine expression of the proinflammatory cytokines IL-6 and IL-8.Cancer Res 73, no. 11 (June 1, 2013): 3470–80. https://doi.org/10.1158/0008-5472.CAN-12-4524-T.
Hartman ZC, Poage GM, den Hollander P, Tsimelzon A, Hill J, Panupinthu N, et al. Growth of triple-negative breast cancer cells relies upon coordinate autocrine expression of the proinflammatory cytokines IL-6 and IL-8. Cancer Res. 2013 Jun 1;73(11):3470–80.
Hartman, Zachary C., et al. “Growth of triple-negative breast cancer cells relies upon coordinate autocrine expression of the proinflammatory cytokines IL-6 and IL-8.Cancer Res, vol. 73, no. 11, June 2013, pp. 3470–80. Pubmed, doi: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. Growth of triple-negative breast cancer cells relies upon coordinate autocrine expression of the proinflammatory cytokines IL-6 and IL-8. Cancer Res. 2013 Jun 1;73(11):3470–3480.

Published In

Cancer Res

DOI

EISSN

1538-7445

Publication Date

June 1, 2013

Volume

73

Issue

11

Start / End Page

3470 / 3480

Location

United States

Related Subject Headings

  • Triple Negative Breast Neoplasms
  • Transfection
  • Signal Transduction
  • Proportional Hazards Models
  • Oncology & Carcinogenesis
  • Neoplastic Stem Cells
  • Mice, Nude
  • Mice
  • Interleukin-8
  • Interleukin-6