Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Cell Motility Is Decreased in Macrophages Activated by Cancer Cell-Conditioned Medium

  • Go, Ahreum (Department of Bioscience and Biotechnology, Sejong University) ;
  • Ryu, Yun-Kyoung (Department of Bioscience and Biotechnology, Sejong University) ;
  • Lee, Jae-Wook (Department of Bioscience and Biotechnology, Sejong University) ;
  • Moon, Eun-Yi (Department of Bioscience and Biotechnology, Sejong University)
  • Received : 2013.09.26
  • Accepted : 2013.11.11
  • Published : 2013.11.30
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Abstract

Macrophages play a role in innate immune responses to various foreign antigens. Many products from primary tumors influence the activation and transmigration of macrophages. Here, we investigated a migration of macrophages stimulated with cancer cell culture-conditioned medium (CM). Macrophage activation by treatment with CM of B16F10 cells were judged by the increase in protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2). The location where macrophages were at 4 h-incubation with control medium or CM was different from where they were at 5 h-incubation in culture dish. Percentage of superimposed macrophages at every 1 h interval was gradually increased by CM treatment as compared to control. Total coverage of migrated track expressed in coordinates was smaller and total distance of migration was shorter in CM-treated macrophages than that in control. Rac1 activity in CM-treated macrophages was also decreased as compared to that in control. When macrophages were treated with CM in the presence of dexamethasone (Dex), an increase in COX2 protein levels, and a decrease in Rac1 activity and total coverage of migration were reversed. In the meanwhile, biphasic changes were detected by Dex treatment in section distance of migration at each time interval, which was more decreased at early time and then increased at later time. Taken together, data demonstrate that macrophage motility could be reduced in accordance with activation in response to cancer cell products. It suggests that macrophage motility could be a novel marker to monitor cancer-associated inflammatory diseases and the efficacy of anti-inflammatory agents.

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References

  1. Aflaki, E., Balenga, N. A., Luschnig-Schratl, P., Wolinski, H., Povoden, S., Chandak, P. G., Bogner-Strauss, J. G., Eder, S., Konya, V., Kohlwein, S. D., Heinemann, A. and Kratky, D. (2011) Impaired Rho GTPase activation abrogates cell polarization and migration in macrophages with defective lipolysis. Cell. Mol. Life Sci. 68, 3933-3947. https://doi.org/10.1007/s00018-011-0688-4
  2. Bailey, C. L., Kelly, P. and Casey, P. J. (2009) Activation of Rap1 promotes prostate cancer metastasis. Cancer Res. 69, 4962-4968. https://doi.org/10.1158/0008-5472.CAN-08-4269
  3. Balkwill, F., Charles, K. A. and Mantovani, A. (2005) Smoldering and polarized inflammation in the initiation and promotion of malignant disease. Cancer Cell 7, 211-217. https://doi.org/10.1016/j.ccr.2005.02.013
  4. Baruzzi, A., Caveggion, E. and Berton, G. (2008) Regulation of phagocyte migration and recruitment by Src-family kinases. Cell. Mol. Life Sci. 65, 2175-2190. https://doi.org/10.1007/s00018-008-8005-6
  5. Borisy, G. G. and Svitkina, T. M. (2000) Actin machinery: pushing the envelope. Curr. Opin. Cell Biol. 12, 104-112. https://doi.org/10.1016/S0955-0674(99)00063-0
  6. Bos, J. L., de Rooij, J. and Reedquist, K. A. (2001) Rap1 signalling: adhering to new models. Nat. Rev. Mol. Cell Biol. 2, 369-377. https://doi.org/10.1038/35073073
  7. Chen, H., Bernstein, B. W. and Bamburg, J. R. (2000) Regulating actin-filament dynamics in vivo. Trends Biochem. Sci. 25, 19-23. https://doi.org/10.1016/S0968-0004(99)01511-X
  8. Condeelis, J. and Pollard, J. W. (2006) Macrophages: obligate partners for tumor cell migration, invasion, and metastasis. Cell 124, 263-266. https://doi.org/10.1016/j.cell.2006.01.007
  9. Cougoule, C., Le Cabec, V., Poincloux, R., Al Saati, T., Mege, J. L., Tabouret, G., Lowell, C. A., Laviolette-Malirat, N. and Maridonneau- Parini, I. (2010) Three-dimensional migration of macrophages requires Hck for podosome organization and extracellular matrix proteolysis. Blood 115, 1444-1452. https://doi.org/10.1182/blood-2009-04-218735
  10. Geissmann, F., Manz, M. G., Jung, S., Sieweke, M. H., Merad, M. and Ley, K. (2010) Development of monocytes, macrophages, and dendritic cells. Science 327, 656-661. https://doi.org/10.1126/science.1178331
  11. Gong, Y., Hart, E., Shchurin, A. and Hoover-Plow, J. (2008) Inflammatory macrophage migration requires MMP-9 activation by plasminogen in mice. J. Clin. Invest. 118, 3012-3024. https://doi.org/10.1172/JCI32750
  12. Gordon, S. (2002) Pattern recognition receptors: doubling up for the innate immune response. Cell 111, 927-930. https://doi.org/10.1016/S0092-8674(02)01201-1
  13. Hiratsuka, S., Watanabe, A., Aburatani, H. and Maru, Y. (2006) Tumour- mediated upregulation of chemoattractants and recruitment of myeloid cells predetermines lung metastasis. Nat. Cell Biol. 8, 1369-1375. https://doi.org/10.1038/ncb1507
  14. Kometani, K., Ishida, D., Hattori, M. and Minato, N. (2004) Rap1 and SPA-1 in hematologic malignancy. Trends Mol. Med. 10, 401-408. https://doi.org/10.1016/j.molmed.2004.06.004
  15. Lauffenburger, D. A. and Horwitz, A. F. (1996) Cell migration: a physically integrated molecular process. Cell 84, 359-369. https://doi.org/10.1016/S0092-8674(00)81280-5
  16. Luedde, T. (2010) MicroRNA-151 and its hosting gene FAK (focal adhesion kinase) regulate tumor cell migration and spreading of hepatocellular carcinoma. Hepatology 52, 1164-1166.
  17. Luster, A. D., Alon, R. and von Andrian, U. H. (2005) Immune cell migration in inflammation: present and future therapeutic targets. Nat. Immunol. 6, 1182-1190. https://doi.org/10.1038/ni1275
  18. Mackay, C. R. (2008) Moving targets: cell migration inhibitors as new anti-inflammatory therapies. Nat. Immunol. 9, 988-998. https://doi.org/10.1038/ni.f.210
  19. Mantovani, A., Allavena, P., Sica, A. and Balkwill, F. (2008) Cancerrelated inflammation. Nature 454, 436-444. https://doi.org/10.1038/nature07205
  20. Medzhitov, R. (2008) Origin and physiological roles of inflammation. Nature 454, 428-435. https://doi.org/10.1038/nature07201
  21. Singer, S. J. and Kupfer, A. (1986) The directed migration of eukaryotic cells. Annu. Rev. Cell Biol. 2, 337-365. https://doi.org/10.1146/annurev.cb.02.110186.002005
  22. Takai, Y., Sasaki, T. and Matozaki, T. (2001) Small GTP-binding proteins. Physiol. Rev. 81, 153-208. https://doi.org/10.1152/physrev.2001.81.1.153
  23. Takai, Y., Sasaki, T., Tanaka, K. and Nakanishi, H. (1995) Rho as a regulator of the cytoskeleton. Trends Biochem. Sci. 20, 227-231. https://doi.org/10.1016/S0968-0004(00)89022-2
  24. Webb, D. J., Parsons, J. T. and Horwitz, A. F. (2002) Adhesion assembly, disassembly and turnover in migrating cells -- over and over and over again. Nat. Cell Biol. 4, E97-100. https://doi.org/10.1038/ncb0402-e97
  25. Yamazaki, D., Kurisu, S. and Takenawa, T. (2005) Regulation of cancer cell motility through actin reorganization. Cancer Sci. 96, 379-386. https://doi.org/10.1111/j.1349-7006.2005.00062.x

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