Normal mammary epithelial cells promote carcinoma basement membrane invasion by inducing microtubule-rich protrusions

Oncotarget. 2015 Oct 20;6(32):32634-45. doi: 10.18632/oncotarget.4728.

Abstract

Recent work suggests that the dissemination of tumor cells may occur in parallel with, and even preceed, tumor growth. The mechanism for this early invasion is largely unknown. Here, we find that mammary epithelial cells (MECs) induce neighboring breast carcinoma cells (BCCs) to cross the basement membrane by secreting soluble laminin. Laminin continuously produced by MECs induce long membrane cellular protrusions in BCCs that promote their contractility and invasion into the surrounding matrix. These protrusions depend on microtubule bundles assembled de novo through laminin-integrin β1 signaling. These results describe how non-cancerous MECs can actively participate in the invasive process of BCCs.

Keywords: cancer invasion; cell-cell interaction; laminin; microtubule; protrusion.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Basement Membrane / metabolism*
  • Basement Membrane / pathology
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Carcinoma / genetics
  • Carcinoma / metabolism*
  • Carcinoma / mortality
  • Carcinoma / secondary
  • Cell Line
  • Cell Movement*
  • Cell Surface Extensions / metabolism*
  • Cell Surface Extensions / pathology
  • Coculture Techniques
  • Epithelial Cells / metabolism*
  • Epithelial Cells / pathology
  • Female
  • Humans
  • Integrin beta1 / genetics
  • Integrin beta1 / metabolism
  • Kaplan-Meier Estimate
  • Laminin / metabolism*
  • Mammary Glands, Human / metabolism*
  • Mammary Glands, Human / pathology
  • Microtubules / metabolism*
  • Microtubules / pathology
  • Neoplasm Invasiveness
  • Paracrine Communication*
  • Phenotype
  • Prognosis
  • Signal Transduction
  • Solubility
  • Time Factors
  • Transfection

Substances

  • Integrin beta1
  • Laminin