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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

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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 mm 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 a4, a5, av and b1 integrins, which mediate FN attachment, were expressed on positively and negatively selected sub-lines and parental CT 26 cells. Activation of integrins with Mn 2+ 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 sig-nificant 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.© Kluwer Academic Publishers 1998

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Authors and Affiliations

  1. Department of Life Sciences, Nottingham Trent University, Clifton Lane, Nottingham, UK

    Li Geng

  2. Department of Life Sciences, Nottingham Trent University, Clifton Lane, Nottingham, UK

    Selman A Ali, C. Logan Mackay & Robert C Rees

  3. Richard Dimbleby Department of Cancer Research/Imperial Cancer Research Fund, The Rayne Institute, United Medical and Dental Schools, St. Thomas' Hospital, Lambeth Palace Road, London, UK

    John F Marshall & Ian R Hart

  4. School of Biological Sciences, University of Manchester, Oxford Road, Manchester, UK

    Marc Delcommence & Charles H Streuli

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  1. Li Geng
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  2. Selman A Ali
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  4. C. Logan Mackay
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  6. Marc Delcommence
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  7. Charles H Streuli
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  8. Robert C Rees
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Geng, L., Ali, S.A., Marshall, J.F. et al. Fibronectin is chemotactic for CT 26 colon carcinoma cells: sub-lines selected for increased chemotaxis to fibronectin display decreased tumorigenicity and lung colonization. Clin Exp Metastasis 16, 683–691 (1998). https://doi.org/10.1023/A:1006572526520

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