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Fibronectin is chemotactic for CT 26 colon carcinoma cells: sub-lines selected for increased chemotaxis to fibronectin display decreased tumorigenicity and lung colonization

Authors
Publication Date
Keywords
  • Adenocarcinoma/*Pathology/*Secondary
  • Animals
  • Cell Adhesion/Drug Effects/Physiology
  • Cell Division/Drug Effects
  • Cell Transformation
  • Neoplastic/*Pathology
  • Chemotactic Factors/*Physiology
  • *Chemotaxis/Drug Effects
  • Collagen/Pharmacology
  • Colonic Neoplasms/*Pathology
  • Extracellular Matrix Proteins/Metabolism
  • Fibronectins/*Physiology
  • Laminin/Pharmacology
  • Lung Neoplasms/*Secondary
  • Mice
  • Tumor Cells
  • Cultured
Disciplines
  • Medicine

Abstract

CT 26 murine colon carcinoma cells demonstrated directional migration (chemotaxis) in response to fibronectin (FN). Sub-lines were derived by positive and negative selection to FN across Transwell filters of 8 microm pore size. The FL6 sub-line (positively selected) demonstrated a significantly increased chemotactic response (P<0.01) to FN compared with parental CT 26 cells, while the FU7 sub-line (negatively selected) showed a reduced chemotactic response to FN (P<0.01). Comparable levels of alpha4, alpha5, alphav and beta1 integrins, which mediate FN attachment, were expressed on positively and negatively selected sub-lines and parental CT 26 cells. Activation of integrins with Mn2+ suggested that the integrins expressed on FL6 cells were in the fully activated state; in contrast FU7 cells displayed only partially activated integrins. Cell attachment and integrin activation status of the sub-lines correlated with their chemotactic response to FN. In vivo FL6 cells showed a significantly reduced tumour growth rate s.c. and a reduction in the number of lung colonies formed following i.v. injection compared with parental CT 26 and FU7 cells. In contrast FU7 cells displayed a significant increase in s.c. tumour growth and the number of lung colonies when compared with the parental line and FL6 sub-line. The results indicate that interaction between integrin receptors expressed on cancer cells and FN plays a central role in the chemotactic response of CT 26 colon carcinoma cells, and that in this model cells selected for chemotaxis to FN displayed a reduced malignant potential.

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