Abstract
The interaction between stromal cells and tumor cells is emerging as a critical aspect of tumor progression. Yet there is a paucity of molecular markers for cells participating in such interactions, and only few genes are known to play a critical role in this process. Here, we describe the identification of ADAM12 (a disintegrin and metalloprotease 12) as a novel marker for a subpopulation of stromal cells that are adjacent to epithelial tumor cells in three mouse carcinoma models (models for prostate, breast and colon cancer). Moreover, we show that ADAM12 is essential for tumor development and progression in the W10 mouse model for prostate cancer. These results suggest that ADAM12 might be a useful marker for stromal cells in mouse tumors that are likely to participate in stromal/tumor cell crosstalk, and that ADAM12 is a potential target for design of drugs that prevent carcinoma growth.
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References
Adam RM, Kim J, Lin J, Orsola A, Zhuang L, Rice DC et al. (2002). Endocrinology 143: 4599–4608.
Asakura M, Kitakaze M, Takashima S, Liao Y, Ishikura F, Yoshinaka T et al. (2002). Nat Med 8: 35–40.
Bhowmick NA, Neilson EG, Moses HL . (2004). Nature 432: 332–337.
Blobel CP . (2005). Nat Rev Mol Cell Biol 6: 32–43.
Cunha GR, Hayward SW, Wang YZ, Ricke WA . (2003). Int J Cancer 107: 1–10.
Desmouliere A, Guyot C, Gabbiani G . (2004). Int J Dev Biol 48: 509–517.
Freeman MR, Paul S, Kaefer M, Ishikawa M, Adam RM, Renshaw AA et al. (1998). J Cell Biochem 68: 328–338.
Guy CT, Cardiff RD, Muller WJ . (1992). Mol Cell Biol 12: 954–961.
Iba K, Albrechtsen R, Gilpin BJ, Loechel F, Wewer UM . (1999). Am J Pathol 154: 1489–1501.
Kodama T, Ikeda E, Okada A, Ohtsuka T, Shimoda M, Shiomi T et al. (2004). Am J Pathol 165: 1743–1753.
Kurisaki T, Masuda A, Osumi N, Nabeshima Y, Fujisawa-Sehara A . (1998). Mech Dev 73: 211–215.
Kveiborg M, Frohlich C, Albrechtsen R, Tischler V, Dietrich N, Holck P et al. (2005). Cancer Res 65: 4754–4761.
Le Pabic H, Bonnier D, Wewer UM, Coutand A, Musso O, Baffet G et al. (2003). Hepatology 37: 1056–1066.
Loechel F, Fox JW, Murphy G, Albrechtsen R, Wewer UM . (2000). Biochem Biophys Res Commun 278: 511–515.
Lu Z, Ghosh S, Wang Z, Hunter T . (2003). Cancer Cell 4: 499–515.
Manova K, Bachvarova RF, Huang EJ, Sanchez S, Pronovost SM, Velazquez E et al. (1992). J Neurosci 12: 4663–4676.
Moser AR, Pitot HC, Dove WF . (1990). Science 247: 322–324.
Peduto L, Reuter VE, Shaffer DR, Scher HI, Blobel CP . (2005). Cancer Res 65: 9312–9319.
Schuurmans AL, Bolt J, Mulder E . (1988). Mol Cell Endocrinol 60: 101–104.
Shaffer DR, Viale A, Ishiwata R, Leversha M, Olgac S, Manova K et al. (2005). Proc Natl Acad Sci USA 102: 210–215.
Shappell SB, Thomas GV, Roberts RL, Herbert R, Ittmann MM, Rubin MA et al. (2004). Cancer Res 64: 2270–2305.
Torring N, Moller-Ernst Jensen K, Lund L, Nielsen JE, Djurhuus JC, Poulsen SS et al. (2002). BJU Int 89: 583–590.
Acknowledgements
We thank Dr A Koff for W10 mice, Drs B Fingleton and L Matrisian for tumors from MMTV-PyMT and Apc/Min/+ mice, and Brian Hutchinson and Katia Bozhilova for excellent technical assistance. This investigation was conducted in a facility constructed with support from Research Facilities Improvement Program Grant Number C06-RR12538-01 from the National Center for Research Resources, National Institutes of Health. Financial Support was provided by the Koch and Pepsico Funds to CPB, HS and LP, and by NIH-GM64750 to CPB.
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Peduto, L., Reuter, V., Sehara-Fujisawa, A. et al. ADAM12 is highly expressed in carcinoma-associated stroma and is required for mouse prostate tumor progression. Oncogene 25, 5462–5466 (2006). https://doi.org/10.1038/sj.onc.1209536
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DOI: https://doi.org/10.1038/sj.onc.1209536
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