Tissue architecture and function: Dynamic reciprocity via extra- and intra-cellular matrices

Ren Xu, Aaron Boudreau, Mina J. Bissell

Research output: Contribution to journalReview articlepeer-review

247 Scopus citations


Mammary gland development, functional differentiation, and homeostasis are orchestrated and sustained by a balance of biochemical and biophysical cues from the organ's microenvironment. The three-dimensional microenvironment of the mammary gland, predominantly 'encoded' by a collaboration between the extracellular matrix (ECM), hormones, and growth factors, sends signals from ECM receptors through the cytoskeletal intracellular matrix to nuclear and chromatin structures resulting in gene expression; the ECM in turn is regulated and remodeled by signals from the nucleus. In this chapter, we discuss how coordinated ECM deposition and remodeling is necessary for mammary gland development, how the ECM provides structural and biochemical cues necessary for tissue-specific function, and the role of the cytoskeleton in mediating the extra-to intracellular dialogue occurring between the nucleus and the microenvironment. When operating normally, the cytoskeletal-mediated dynamic and reciprocal integration of tissue architecture and function directs mammary gland development, tissue polarity, and ultimately, tissue-specific gene expression. Cancer occurs when these dynamic interactions go awry for an extended time.

Original languageEnglish
Pages (from-to)167-176
Number of pages10
JournalCancer and Metastasis Reviews
Issue number1-2
StatePublished - 2009

Bibliographical note

Funding Information:
Acknowledgements We apologize to those whose work could not be cited due to space limitations. This work was supported by the Office of Biological and Environmental Research of the Department of Energy (DOE-AC03-76SF00098), the National Institutes of Health (CA112970-01), (R01CA057621) to Zena Werb and M.J.B., (R01CA064786) to M.J.B. and the Breast Cancer Research Program (BCRP) of the Department of Defense (DOD) (Innovator Award) to M.J.B. M.JB. is a Distinguished Scientist of the OBER Office of the DOE. Support was also provided by a DOD BCRP postdoctoral fellowship DAMD17-02-1-0441 to R.X., a predoctoral fellowship W81XWH-05-1-0339 to A.T.B, and by a California BCRP Dissertation Award to ATB.


  • Acinar morphogenesis
  • Chromatin organization
  • Cytoskeleton
  • Extracellular matrix
  • Mammary-specific function
  • Microenvironment
  • Tissue architecture

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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