Introduction The prognosis of patients with cancer is influenced by tumour growth, local invasion, and metastasis, and these processes are determined, in part, by the interaction of tumour cells with the extracellular matrix (ECM) [1,2]. Most malignant cells fail to deposit ECM components such as fibronectin (FN) [3–5], and as a consequence mobility of tumour cells is not limited by adhesion to the molecules within their microenvironment. Cells interact with FN through specific cell surface receptors, which belong, in the main, to the integrin family. The typical FN receptor is a non-covalent complex of a larger 5 subunit of 145 kDa and a smaller 1 subunit of 125 kDa [6]. Other integrins, including 31 [7], 11111 2 3 4 5 6 7 8 9 10111 1 2 3 4 5 6 7 8 9 20111 1 2 3 4 5 6 7 8 9 30111 1 2 3 4 5 6 7 8 9 40111 1 2 3 4 5 6 7 8 9 50111 1 2 3 4111 Clin. Exp. Metastasis, 1998, 16, 683–691 © 1998 Kluwer Academic Publishers Clinical & Experimental Metastasis Vol 16 No 8 683 Fibronectin is chemotactic for CT 26 colon carcinoma cells: sub-lines selected for increased chemotaxis to fibronectin display decreased tumorigenicity and lung colonization Li Geng 1 , Selman A. Ali 1 , John F. Marshall 2 , C. Logan Mackay 1 , Ian R. Hart 2 , Marc Delcommence 3 , Charles H. Streuli 3 and Robert C. Rees 1 1 Department of Life Sciences, Nottingham Trent University, Clifton Lane, Nottingham; 2 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; 3 School of Biological Sciences, University of Manchester, Oxford Road, Manchester, UK (Received 5 February 1998; accepted in revised form 20 May 1998) 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 m 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 4, 5, v and 1 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. Keywords: chemotaxis, colon cancer, fibronectin, metastasis, tumorigenicity Address correspondence to: Dr Li Geng, Department of Life Sciences, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NF, UK. Tel: (+44) 115 848 3078. Fax: (+44) 115 948 6636.