Choreographing metastasis to the tune of LTBP

J Mammary Gland Biol Neoplasia. 2011 Jun;16(2):67-80. doi: 10.1007/s10911-011-9215-3. Epub 2011 Apr 15.

Abstract

Latent Transforming Growth Factor beta (TGFβ) Binding Proteins (LTBPs) are chaperones and determinants of TGFβ isoform-specific secretion. They belong to the LTBP/Fibrillin family and form integral components of the fibronectin and microfibrillar extracellular matrix (ECM). LTBPs serve as master regulators of TGFβ bioavailability, functioning to incorporate and spatially pattern latent TGFβ at regular intervals within the ECM, and actively participate in integrin-mediated stretch activation of TGFβ in vivo. In so doing they create a highly patterned sensory system where local changes in ECM tension can be detected and transduced into focal signals. The physiological role of LTBPs in the mammary gland remains largely unstudied, however both loss and gain of LTBP expression is found in breast cancers and breast cancer cell lines. Importantly, elevated LTBP1 levels appear in two gene signatures predictive of enhanced metastatic behavior. LTBP may promote metastasis by providing the bridge between structural and signaling components of the epithelial to mesenchymal transition (EMT).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Female
  • Humans
  • Latent TGF-beta Binding Proteins / genetics
  • Latent TGF-beta Binding Proteins / metabolism*
  • Mammary Glands, Animal / metabolism*
  • Mammary Glands, Animal / physiology
  • Mammary Glands, Human / metabolism*
  • Mammary Glands, Human / physiology
  • Mammary Neoplasms, Experimental / genetics
  • Mammary Neoplasms, Experimental / metabolism
  • Mammary Neoplasms, Experimental / pathology*
  • Mice
  • Neoplasm Metastasis
  • Signal Transduction
  • Transforming Growth Factor beta / metabolism*

Substances

  • Latent TGF-beta Binding Proteins
  • Transforming Growth Factor beta