Extracellular acidification alters lysosomal trafficking in human breast cancer cells

Neoplasia. Nov-Dec 2003;5(6):533-45. doi: 10.1016/s1476-5586(03)80037-4.

Abstract

Cancer cells invade by secreting degradative enzymes, which are sequestered in lysosomal vesicles. In this study, the impact of an acidic extracellular environment on lysosome size, number, and distance from the nucleus in human mammary epithelial cells (HMECs) and breast cancer cells of different degrees of malignancy was characterized because the physiological microenvironment of tumors is frequently characterized by extracellular acidity. An acidic extracellular pH (pH(e)) resulted in a distinct shift of lysosomes from the perinuclear region to the cell periphery irrespective of the HMECs' degree of malignancy. With decreasing pH, larger lysosomal vesicles were observed more frequently in highly metastatic breast cancer cells, whereas smaller lysosomes were observed in poorly metastatic breast cancer cells and HMECs. The number of lysosomes decreased with acidic pH values. The displacement of lysosomes to the cell periphery driven by extracellular acidosis may facilitate exocytosis of these lysosomes and increase secretion of degradative enzymes. Filopodia formations, which were observed more frequently in highly metastatic breast cancer cells maintained at acidic pH(e), may also contribute to invasion.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, CD / metabolism
  • Blotting, Western
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / ultrastructure
  • Cell Line, Tumor
  • Extracellular Fluid / chemistry*
  • Fluorescent Antibody Technique
  • Humans
  • Hydrogen-Ion Concentration
  • Image Processing, Computer-Assisted
  • Lysosome-Associated Membrane Glycoproteins
  • Lysosomes / metabolism*
  • Lysosomes / ultrastructure
  • Mammary Glands, Human / metabolism*
  • Mammary Glands, Human / ultrastructure
  • Microscopy, Confocal
  • Neoplasm Invasiveness
  • Protein Transport / physiology

Substances

  • Antigens, CD
  • Lysosome-Associated Membrane Glycoproteins