The role of fibrosis in tumor progression and the dormant to proliferative switch

Lara H. El Touny, Dalit Barkan, Jeffrey E. Green

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review


The extracellular matrix is known to play a pivotal role in normal breast development as well as tumorigenesis and breast cancer progression. Several lines of clinical evidence have associated the presence of fi brotic-like, activated stroma with poor therapeutic response and prognosis in breast cancer patients. Recent evidence suggests that extracellular changes are requisite for the formation of a pre-metastatic niche that provides a permissive environment for disseminated breast cancer cells to survive and proliferate. It is also thought that in the absence of favorable environmental cues at a metastatic site, disseminated tumor cells can be maintained in a dormant, metabolically active state until they encounter or modulate their surroundings into an environment that supports their proliferation. We have shown in vivo that the induction of lung fi brosis via adenoviral instillation of TGFß, which results in collagen-I accumulation, can induce the proliferation of an otherwise dormant breast cancer cell line (D2.0R). We have recapitulated this dormant-toproliferative switch by collagen-I supplementation in a three dimensional in vitro model of dormancy, suggesting that collagen-I is a major contributor to the overtly proliferative integrin β1-dependent state of the D2.0R cells in fi brotic lungs. This work has highlighted the importance of the integrin β1 pathway and its downstream effectors as principal playersin sensing microenvironmental changes by dormant breast cells and activating proproliferative pathways resulting in overt metastases.

Original languageEnglish
Title of host publicationTumor Dormancy, Quiescence, and Senescence, Volume 2
Subtitle of host publicationAging, Cancer, and Noncancer Pathologies
PublisherSpringer Netherlands
Number of pages10
ISBN (Electronic)9789400777262
ISBN (Print)9789400777255
StatePublished - 1 Jan 2014

Bibliographical note

Publisher Copyright:
© Springer Science+Business Media Dordrecht 2014.


  • Breast cancer
  • Cancer-associated fibroblast (CAF)
  • Collagen-I and breast cancer dormancy
  • Extracellular matrix (ECM)
  • Fibrosis
  • Hypoxia inducible factor (HIF)
  • Lysyl oxidase (LOX)
  • Proliferative switch
  • Tumor progression and dormancy
  • VEGF receptor(VEGFR)

ASJC Scopus subject areas

  • General Agricultural and Biological Sciences
  • General Biochemistry, Genetics and Molecular Biology
  • General Medicine


Dive into the research topics of 'The role of fibrosis in tumor progression and the dormant to proliferative switch'. Together they form a unique fingerprint.

Cite this