Breast Cancer Research and Treatment

, Volume 114, Issue 1, pp 47–62 | Cite as

Molecular signatures suggest a major role for stromal cells in development of invasive breast cancer

  • Theresa Casey
  • Jeffrey Bond
  • Scott Tighe
  • Timothy Hunter
  • Laura Lintault
  • Osman Patel
  • Jonathan Eneman
  • Abigail Crocker
  • Jeffrey White
  • Joseph Tessitore
  • Mary Stanley
  • Seth Harlow
  • Donald Weaver
  • Hyman Muss
  • Karen Plaut
Preclinical Study

Abstract

Background Breast cancer invasion and metastasis involves both epithelial and stromal changes. Our objective was to delineate the pivotal role stroma plays in invasion by comparing transcriptomes among stromal and epithelial cells in normal tissue and invasive breast cancer. Methods Total RNA was isolated from epithelial and stromal cells that were laser captured from normal breast tissue (n = 5) and invasive breast cancer (n = 28). Gene expression was measured using Affymetrix U133A 2.0 GeneChips. Differential gene expression was evaluated and compared within a model that accounted for cell type (epithelial [E] versus stromal [S]), diagnosis (cancer [C] versus normal [N]) as well as cell type-diagnosis interactions. Results Compared to NE, the CE transcriptome was highly enriched with genes in proliferative, motility and ECM ontologies. Differences in CS and NS transcriptomes suggested that the ECM was being remodeled in invasive breast cancer, as genes were over-represented in ECM and proteolytic ontologies. Genes more highly expressed in CS compared to CE were primarily ECM components or were involved in the remodeling of ECM, suggesting that ECM biosynthesis and remodeling were initiated in the tumor stroma. Conclusion Based on identified molecular cross-talk between the two contiguous cell populations, a mechanistic model that spurs invasion is proposed, that shows breast cancer invasion proceeds through the acquisition of a motile phenotype in tumor epithelial cells and a reactive phenotype in cancer associated fibroblasts.

Keywords

Epithelium Invasion Microarray analysis Stroma Transcriptome 

Abbreviations

NE

Normal epithelium

NS

Normal stroma

CE

Cancer epithelium

CS

Cancer stroma

LCM

Laser capture microdissection

EMT

Epithelial to mesenchyme transdifferentiation

Notes

Acknowledgements

This work was supported by a grant from the Breast Cancer Research Foundation; New York, N.Y. Microarray analysis was performed in the University of Vermont Microarray Facility and was supported in part by grant P30CA22435 from the NCI.

Supplementary material

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10549_2008_9982_MOESM2_ESM.doc (32 kb)
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10549_2008_9982_MOESM3_ESM.doc (37 kb)
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Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Theresa Casey
    • 1
    • 2
  • Jeffrey Bond
    • 3
  • Scott Tighe
    • 4
  • Timothy Hunter
    • 4
  • Laura Lintault
    • 1
  • Osman Patel
    • 2
  • Jonathan Eneman
    • 5
  • Abigail Crocker
    • 5
  • Jeffrey White
    • 1
  • Joseph Tessitore
    • 6
  • Mary Stanley
    • 7
  • Seth Harlow
    • 7
  • Donald Weaver
    • 6
  • Hyman Muss
    • 5
  • Karen Plaut
    • 2
  1. 1.Animal ScienceUniversity of VermontBurlingtonUSA
  2. 2.Animal ScienceMichigan State UniversityEast LansingUSA
  3. 3.Vermont Cancer Center Bioinformatics CoreUniversity of VermontBurlingtonUSA
  4. 4.University of Vermont Microarray Core Facility, University of VermontBurlingtonUSA
  5. 5.Hematology and OncologyUniversity of VermontBurlingtonUSA
  6. 6.PathologyUniversity of VermontBurlingtonUSA
  7. 7.SurgeryUniversity of VermontBurlingtonUSA

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