Cancer-Associated Fibroblasts Are Activated in Incipient Neoplasia to Orchestrate Tumor-Promoting Inflammation in an NF-kappaB-Dependent Manner - PubMed

Affiliations

• PMID: 20138012
• DOI: 10.1016/j.ccr.2009.12.041

Free article

Cancer-Associated Fibroblasts Are Activated in Incipient Neoplasia to Orchestrate Tumor-Promoting Inflammation in an NF-kappaB-Dependent Manner

Neta Erez et al. Cancer Cell. 2010.

Free article

Erratum in

• Cancer Cell. 2010 May 18;17(5):523. Arron, Sarah Tuttleton [added]

Abstract

Cancer-associated fibroblasts (CAFs) support tumorigenesis by stimulating angiogenesis, cancer cell proliferation, and invasion. We demonstrate that CAFs also mediate tumor-enhancing inflammation. Using a mouse model of squamous skin carcinogenesis, we found a proinflammatory gene signature in CAFs isolated from dysplastic skin. This signature was maintained in CAFs from subsequent skin carcinomas and was evident in mammary and pancreatic tumors in mice and in cognate human cancers. The inflammatory signature was already activated in CAFs isolated from the initial hyperplastic stage in multistep skin tumorigenesis. CAFs from this pathway promoted macrophage recruitment, neovascularization, and tumor growth, activities that are abolished when NF-kappaB signaling was inhibited. Additionally, we show that normal dermal fibroblasts can be "educated" by carcinoma cells to express proinflammatory genes.

Comment in

• La mala educación of tumor-associated macrophages: Diverse pathways and new players.

  Mantovani A. Mantovani A. Cancer Cell. 2010 Feb 17;17(2):111-2. doi: 10.1016/j.ccr.2010.01.019. Cancer Cell. 2010. PMID: 20159603

Similar articles

• Cancer associated fibroblasts express pro-inflammatory factors in human breast and ovarian tumors.

  Erez N, Glanz S, Raz Y, Avivi C, Barshack I. Erez N, et al. Biochem Biophys Res Commun. 2013 Aug 2;437(3):397-402. doi: 10.1016/j.bbrc.2013.06.089. Epub 2013 Jul 2. Biochem Biophys Res Commun. 2013. PMID: 23831470

• Nuclear factor-kappaB is an important modulator of the altered gene expression profile and malignant phenotype in squamous cell carcinoma.

  Loercher A, Lee TL, Ricker JL, Howard A, Geoghegen J, Chen Z, Sunwoo JB, Sitcheran R, Chuang EY, Mitchell JB, Baldwin AS Jr, Van Waes C. Loercher A, et al. Cancer Res. 2004 Sep 15;64(18):6511-23. doi: 10.1158/0008-5472.CAN-04-0852. Cancer Res. 2004. PMID: 15374962

• The canonical NF-kappaB pathway is required for formation of luminal mammary neoplasias and is activated in the mammary progenitor population.

  Pratt MA, Tibbo E, Robertson SJ, Jansson D, Hurst K, Perez-Iratxeta C, Lau R, Niu MY. Pratt MA, et al. Oncogene. 2009 Jul 30;28(30):2710-22. doi: 10.1038/onc.2009.131. Epub 2009 Jun 1. Oncogene. 2009. PMID: 19483731

• From sentinel cells to inflammatory culprits: cancer-associated fibroblasts in tumour-related inflammation.

  Servais C, Erez N. Servais C, et al. J Pathol. 2013 Jan;229(2):198-207. doi: 10.1002/path.4103. Epub 2012 Nov 20. J Pathol. 2013. PMID: 22996812 Review.

• Activation of fibroblasts in cancer stroma.

  Räsänen K, Vaheri A. Räsänen K, et al. Exp Cell Res. 2010 Oct 15;316(17):2713-22. doi: 10.1016/j.yexcr.2010.04.032. Epub 2010 May 6. Exp Cell Res. 2010. PMID: 20451516 Review.

Cited by

• It takes two to tango in the microenvironment!

  Ursini-Siegel J, Park M. Ursini-Siegel J, et al. Breast Cancer Res. 2013 Mar 12;15(2):102. doi: 10.1186/bcr3388. Breast Cancer Res. 2013. PMID: 23510134 Free PMC article.

• Epigenetic silencing of microRNA-149 in cancer-associated fibroblasts mediates prostaglandin E2/interleukin-6 signaling in the tumor microenvironment.

  Li P, Shan JX, Chen XH, Zhang D, Su LP, Huang XY, Yu BQ, Zhi QM, Li CL, Wang YQ, Tomei S, Cai Q, Ji J, Li JF, Chouchane L, Yu YY, Sun FZ, Xu ZH, Liu BY, Zhu ZG. Li P, et al. Cell Res. 2015 May;25(5):588-603. doi: 10.1038/cr.2015.51. Epub 2015 Apr 28. Cell Res. 2015. PMID: 25916550 Free PMC article.

• Therapeutic effects of deleting cancer-associated fibroblasts in cholangiocarcinoma.

  Mertens JC, Fingas CD, Christensen JD, Smoot RL, Bronk SF, Werneburg NW, Gustafson MP, Dietz AB, Roberts LR, Sirica AE, Gores GJ. Mertens JC, et al. Cancer Res. 2013 Jan 15;73(2):897-907. doi: 10.1158/0008-5472.CAN-12-2130. Epub 2012 Dec 5. Cancer Res. 2013. PMID: 23221385 Free PMC article.

• Distinct Transcriptional Changes and Epithelial-Stromal Interactions Are Altered in Early-Stage Colon Cancer Development.

  Mo A, Jackson S, Varma K, Carpino A, Giardina C, Devers TJ, Rosenberg DW. Mo A, et al. Mol Cancer Res. 2016 Sep;14(9):795-804. doi: 10.1158/1541-7786.MCR-16-0156. Epub 2016 Jun 27. Mol Cancer Res. 2016. PMID: 27353028 Free PMC article.

• Macrophage plasticity and polarization: in vivo veritas.

  Sica A, Mantovani A. Sica A, et al. J Clin Invest. 2012 Mar;122(3):787-95. doi: 10.1172/JCI59643. Epub 2012 Mar 1. J Clin Invest. 2012. PMID: 22378047 Free PMC article. Review.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Elsevier Science

• Other Literature Sources

  • H1 Connect
  • The Lens - Patent Citations Database

• Molecular Biology Databases

  • Mouse Genome Informatics (MGI)
  • NIAID Data Ecosystem - Find datasets on Infectious and Immune-mediated Diseases