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Autotaxin (ATX), a potent tumor motogen, augments invasive and metastatic potential of ras-transformed cells


Autotaxin (ATX), an exo-nucleotide pyrophosphatase and phosphodiesterase, was originally isolated as a potent stimulator of tumor cell motility. In order to study whether ATX expression affects motility-dependent processes such as invasion and metastasis, we stably transfected full-length ATX cDNA into two non-expressing cell lines, parental and ras-transformed NIH3T3 (clone7) cells. The effect of ATX secretion on in vitro cell motility was variable. The ras-transformed, ATX-secreting subclones had enhanced motility to ATX as chemoattractant, but there was little difference in the motility responses of NIH3T3 cells transfected with atx, an inactive mutant gene, or empty vector. In MatrigelTM invasion assays, all subclones, which secreted enzymatically active ATX, demonstrated greater spontaneous and ATX-stimulated invasion than appropriate controls. This difference in invasiveness was not caused by differences in gelatinase production, which was constant within each group of transfectants. In vivo studies with athymic nude mice demonstrated that injection of atx-transfected NIH3T3 cells resulted in a weak tumorigenic capacity with few experimental metastases. Combination of ATX expression with ras transformation produced cells with greatly amplified tumorigenesis and metastatic potential compared to ras-transformed controls. Thus, ATX appears to augment cellular characteristics necessary for tumor aggressiveness.

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  • Aznavoorian S, Stracke ML, Parsons J, McClanahan J and Liotta LA . 1996 J Biol Chem 271: 3247–3254.

  • Bachner D, Ahrens M, Schroder D, Hoffmann A, Lauber J, Betat N, Steinert P, Flohe L and Gross G . 1998 Dev Dyn 213: 398–411.

  • Clair T, Lee HY, Liotta LA and Stracke ML . 1997 J Biol Chem 272: 996–1001.

  • Deissler H, Blass-Kampmann S, Bruyneel E, Mareel M and Rajewsky MF . 1999 FASEB J 13: 657–666.

  • Deterre P, Gelman L, Gary-Gouy H, Arrieumerlou C, Berthelier V, Tixier JM, Ktorza S, Goding J, Schmitt C and Bismuth G . 1996 J Immunol 157: 1381–1388.

  • Fuss B, Baba H, Phan T, Tuohy VK and Macklin WB . 1997 J Neurosci 17: 9095–9103.

  • Huang RP, Fan Y, Peng A, Zeng ZL, Reed JC, Adamson ED and Boynton AL . 1998 Int J Cancer 77: 880–886.

  • Ju WD, Velu TJ, Vass WC, Papageorge AG and Lowy DR . 1991 New Biol 3: 380–388.

  • Kawagoe H, Stracke ML, Nakamura H and Sano K . 1997 Cancer Res 57: 2516–2521.

  • Kindler-Rohrborn A, Ahrens O, Liepelt U and Rajewsky MF . 1985 Differentiation 30: 53–60.

  • Kindler-Rohrborn A, Blass-Kampmann S, Lennartz K, Liepelt U, Minwegen R and Rajewsky MF . 1994 Differentiation 57: 215–224.

  • Lee HY, Clair T, Mulvaney PT, Woodhouse EC, Aznavoorian S, Liotta LA and Stracke ML . 1996a J Biol Chem 271: 24408–24412.

  • Lee HY, Murata J, Clair T, Polymeropoulos MH, Torres R, Manrow RE, Liotta LA and Stracke ML . 1996b Biochem Biophys Res Commun 218: 714–719.

  • Liotta LA, Mandler R, Murano G, Katz DA, Gordon RK, Chiang PK and Schiffmann E . 1986 Proc Natl Acad Sci USA 83: 3302–3306.

  • MacDonald NJ, Freije JMP, Stracke ML, Manrow RE and Steeg PS . 1996 J Biol Chem 271: 25107–25116.

  • Mulvaney PT, Stracke ML, Nam SW, Woodhouse E, O'Keefe M, Clair T, Liotta LA, Khaddurah-Daouk R and Schiffmann E . 1998 Int J Cancer 78: 46–52.

  • Murata J, Lee HY, Clair T, Krutzsch HC, Arestad AA, Sobel ME, Liotta LA and Stracke ML . 1994 J Biol Chem 269: 30479–30484.

  • Stefan C, Gijsbers R, Stalmans W and Bollen M . 1999 Biochim Biophys Acta 1450: 45–52.

  • Stracke ML, Clair T and Liotta LA . 1997 Adv Enzyme Regul 37: 135–144.

  • Stracke ML, Krutzsch HC, Unsworth EJ, Arestad A, Cioce V, Schiffmann E and Liotta LA . 1992 J Biol Chem 267: 2524–2529.

  • Takahashi T, Carswell EA and Thorbecke GJ . 1970 J Exp Med 132: 1181–1190.

  • Todaro GJ, Fryling C and De Larco JE . 1980 Proc Natl Acad Sci USA 77: 5258–5262.

  • Woodhouse EC, Chuaqui RF, and Liotta LA . 1997 Cancer 80: 1529–1537.

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We would like to thank Dr Elliott Schiffmann for his contributions to experimental design and his suggestions in the preparation of the manuscript.

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Nam, S., Clair, T., Campo, C. et al. Autotaxin (ATX), a potent tumor motogen, augments invasive and metastatic potential of ras-transformed cells. Oncogene 19, 241–247 (2000).

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