Fibronectin is chemotactic for CT 26 colon carcinoma cells: sub-lines selected for increased chemotaxis to fibronectin display decreased tumorigenicity and lung colonization.
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.
Geng
L
L
Department of Life Sciences, Nottingham Trent University, UK.
Ali
S A
SA
Marshall
J F
JF
Mackay
C L
CL
Hart
I R
IR
Delcommence
M
M
Streuli
C H
CH
Rees
R C
RC
D000230:Adenocarcinoma / Q000473:pathology* / Q000556:secondary*; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D002630:Chemotactic Factors / Q000502:physiology*; D002633:Chemotaxis / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000473:pathology*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005353:Fibronectins / Q000502:physiology*; D007797:Laminin / Q000494:pharmacology; D008175:Lung Neoplasms / Q000556:secondary*; D051379:Mice; D014407:Tumor Cells, Cultured
D002630:Chemotactic Factors; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D007797:Laminin; D003094:Collagen