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Epidermal growth factor promotes a mesenchymal over an amoeboid motility of MDA-MB-231 cells embedded within a 3D collagen matrix

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Abstract.

The receptor of epidermal growth factor (EGFR) critically regulates tumor cell invasion and is a potent therapeutic target for treatment of many types of cancers, including carcinomas and glioblastomas. It is known that EGF regulates cell motility when tumor cells are embedded within a 3D biomatrix. However, roles of EGF in modulating tumor cell motility phenotype are largely unknown. In this article, we report that EGF promotes a mesenchymal over an amoeboid motility phenotype using a malignant breast tumor cell line, MDA-MB-231, embedded within a 3D collagen matrix. Amoeboid cells are rounded in shape, while mesenchymal cells are elongated, and their migrations are governed by a distinctly different set of biomolecules. Using single cell tracking analysis, we also show that EGF promotes cell dissemination through a significant increase in cell persistence along with a moderate increase of speed. The increase of persistence is correlated with the increase of the percentage of the mesenchymal cells within the population. Our work reveals a novel role of microenvironmental cue, EGF, in modulating heterogeneity and plasticity of tumor cell motility phenotype. In addition, it suggests a potential visual cue for diagnosing invasive states of breast cancer cells. This work can be easily extended beyond breast cancer cells.

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References

  1. B.D. Harms, G.M. Bassi, A.R. Horwitz, D.A. Lauffenburger, Biophys. J. 88, 1479 (2005)

    Article  Google Scholar 

  2. G. Fontanini, S. Vignati, D. Bigini, A. Mussi, H. Lucchi, C.A. Angeletti, R. Pingitore, S. Pepe, F. Basolo, G. Bevilacqua, Eur. J. Cancer 31A, 178 (1995)

    Article  Google Scholar 

  3. R.N. Jorissen, F. Walker, N. Pouliot, T.P.J. Garrett, C.W. Ward, A.W. Burgess, Exp. Cell Res. 284, 31 (2003)

    Article  Google Scholar 

  4. L.J. McCawley, P. OBrien, L.G. Hudson, Endocrinology 138, 121 (1997)

    Google Scholar 

  5. T. Turner, P. Chen, L.J. Goodly, A. Wells, Clin. Exp. Metastas. 14, 409 (1996)

    Article  Google Scholar 

  6. B.S. Verbeek, S.S. Adriaansen-Slot, T.M. Vroom, T. Beckers, G. Rijksen, Febs. Lett. 425, 145 (1998)

    Article  Google Scholar 

  7. A. Wells, J. Kassis, J. Solava, T. Turner, D.A. Lauffenburger, Acta Oncol. 41, 124 (2002)

    Article  Google Scholar 

  8. M.F. Ware, A. Wells, D.A. Lauffenburger, J. Cell Sci. 111, 2423 (1998)

    Google Scholar 

  9. S. Hart, O.M. Fischer, N. Prenzel, E. Zwick-Wallasch, M. Schneider, L. Hennighausen, A. Ullrich, Biol. Chem. 386, 845 (2005)

    Article  Google Scholar 

  10. Q. Huang, H.M. Shen, C.N. Ong, Cell. Mol. Life Sci. 62, 1167 (2005)

    Article  Google Scholar 

  11. B.J. Kim, P. Hannanta-Anan, M. Chau, Y.S. Kim, M.A. Swartz, M.M. Wu, Plos One 8, e68422 (2013)

    Article  ADS  Google Scholar 

  12. J.S. Krueger, V.G. Keshamouni, N. Atanaskova, K.B. Reddy, Oncogene 20, 4209 (2001)

    Article  Google Scholar 

  13. A.S. Meyer, S.K. Hughes-Alford, J.E. Kay, A. Castillo, A. Wells, F.B. Gertler, D.A. Lauffenburger, J. Cell. Biol. 197, 721 (2012)

    Article  Google Scholar 

  14. J.T. Price, T. Tiganis, A. Agarwal, D. Djakiew, E.W. Thompson, Cancer Res. 59, 5475 (1999)

    Google Scholar 

  15. W.K. Raja, B. Gligorijevic, J. Wyckoff, J.S. Condeelis, J. Castracane, Integr. Biol. Quantit. Biosci. nano macro 2, 696 (2010)

    Google Scholar 

  16. C. Sawyer, J. Sturge, D.C. Bennett, M.J. O’Hare, W.E. Allen, J. Bain, G.E. Jones, B. Vanhaesebroeck, Cancer Res. 63, 1667 (2003)

    Google Scholar 

  17. J.E. Segall, S. Tyerech, L. Boselli, S. Masseling, J. Helft, A. Chan, J. Jones, J. Condeelis, Clin. Exp. Metastas. 14, 61 (1996)

    Article  Google Scholar 

  18. J. Sturge, J. Hamelin, G.E. Jones, J. Cell. Sci. 115, 699 (2002)

    Google Scholar 

  19. R.H. Sun, P. Gao, L. Chen, D.L. Ma, J.M. Wang, J.J. Oppenheim, N. Zhang, Cancer Res. 65, 1433 (2005)

    Article  Google Scholar 

  20. S.J. Wang, W. Saadi, F. Lin, C.M.C. Nguyen, N.L. Jeon, Exp. Cell. Res. 300, 180 (2004)

    Article  Google Scholar 

  21. H.D. Kim, T.W. Guo, A.P. Wu, A. Wells, F.B. Gertler, D.A. Lauffenburger, Mol. Biol. Cell. 19, 4249 (2008)

    Article  Google Scholar 

  22. D.A. Lauffenburger, A.F. Horwitz, Cell 84, 359 (1996)

    Article  Google Scholar 

  23. G. Carpenter, in The EGF Receptor Family, edited by G. Carpenter (Academic Press, Burlington, 2003) pp. 69

  24. J.L. Tan, J. Tien, D.M. Pirone, D.S. Gray, K. Bhadriraju, C.S. Chen, Proc. Natl. Acad. Sci. 100, 1484 (2003)

    Article  ADS  Google Scholar 

  25. Stephanie S. Chang, W.-H. Guo, Y. Kim, Y.-L. Wang, Biophys. J. 104, 313 (2013)

    Article  Google Scholar 

  26. E. Cukierman, R. Pankov, D.R. Stevens, K.M. Yamada, Science 294, 1708 (2001)

    Article  ADS  Google Scholar 

  27. L.G. Griffith, M.A. Swartz, Nat. Rev. Mol. Cell. Biol. 7, 211 (2006)

    Article  Google Scholar 

  28. E. Sahai, C.J. Marshall, Nat. Cell. Biol. 5, 711 (2003)

    Article  Google Scholar 

  29. V. Sanz-Moreno, G. Gadea, J. Ahn, H. Paterson, P. Marra, S. Pinner, E. Sahai, C.J. Marshall, Cell 135, 510 (2008)

    Article  Google Scholar 

  30. T.A. Ulrich, A. Jain, K. Tanner, J.L. MacKay, S. Kumar, Biomaterials 31, 1875 (2010)

    Article  Google Scholar 

  31. K. Wolf, I. Mazo, H. Leung, K. Engelke, U.H. von Andrian, E.I. Deryugina, A.Y. Strongin, E.B. Brocker, P. Friedl, J. Cell. Biol. 160, 267 (2003)

    Article  Google Scholar 

  32. D. Yamazaki, S. Kurisu, T. Takenawa, Oncogene 28, 1570 (2009)

    Article  Google Scholar 

  33. T. Lammermann, B.L. Bader, S.J. Monkley, T. Worbs, R. Wedlich-Soldner, K. Hirsch, M. Keller, R. Forster, D.R. Critchley, R. Fassler et al., Nature 453, 51 (2008)

    Article  ADS  Google Scholar 

  34. K. Pankova, D. Rosel, M. Novotny, J. Brabek, Cell. Mol. Life Sci. 67, 63 (2010)

    Article  Google Scholar 

  35. P. Friedl, J. Locker, E. Sahai, J.E. Segall, Nat. Cell. Biol. 14, 777 (2012)

    Article  Google Scholar 

  36. P. Friedl, K. Wolf, J. Cell Biol. 188, 11 (2010)

    Article  Google Scholar 

  37. J. Condeelis, J.E. Segall, Nat. Rev. Cancer 3, 921 (2003)

    Article  Google Scholar 

  38. W.G. Wang, J.B. Wyckoff, V.C. Frohlich, Y. Oleynikov, S. Huttelmaier, J. Zavadil, L. Cermak, E.P. Bottinger, R.H. Singer, J.G. White et al., Cancer Res. 62, 6278 (2002)

    Google Scholar 

  39. U. Haessler, M. Pisano, M.M. Wu, M.A. Swartz, Proc. Natl. Acad. Sci. U.S.A. 108, 5614 (2011)

    Article  ADS  Google Scholar 

  40. U. Haessler, J.C.M. Teo, D. Foretay, P. Renaud, M.A. Swartz, Integr. Biol. 4, 401 (2012)

    Article  Google Scholar 

  41. M.S. Hall, R. Long, X. Feng, Y. Huang, C.Y. Hui, M. Wu, Exp. Cell. Res. 319, 2396 (2013)

    Article  Google Scholar 

  42. J. Schlessinger, J. Cell. Biol. 103, 2067 (1986)

    Article  Google Scholar 

  43. J. Schlessinger, Biochemistry-Us. 27, 3119 (1988)

    Article  Google Scholar 

  44. R.J. Petrie, N. Gavara, R.S. Chadwick, K.M. Yamada, J. Cell. Biol. 197, 439 (2012)

    Article  Google Scholar 

  45. Y.L. Huang, C.-K. Tung, A. Zheng, B.J. Kim, M. Wu, Integr. Biol. 7, 1402 (2015)

    Article  Google Scholar 

  46. M.L. Taddei, E. Giannoni, A. Morandi, L. Ippolito, M. Ramazzotti, M. Callari, P. Gandellini, P. Chiarugi, Cell. Commun. Signal 12, 24 (2014)

    Article  Google Scholar 

  47. Y.F. Yang, Y.N. Zhao, B. Chen, Q.Q. Han, W.J. Sun, Z.F. Xiao, J.W. Dai, Tissue Eng. A 15, 3589 (2009)

    Article  Google Scholar 

  48. E.T. Roussos, J.S. Condeelis, A. Patsialou, Nat. Rev. Cancer 11, 573 (2011)

    Article  Google Scholar 

  49. A. Wells, Int. J. Biochem. Cell. B 31, 637 (1999)

    Article  Google Scholar 

  50. A.K.V. Iyer, K.T. Tran, L. Griffith, A. Wells, J. Cell. Physiol. 214, 504 (2008)

    Article  Google Scholar 

  51. N.E. Davidson, E.P. Gelmann, M.E. Lippman, R.B. Dickson, Mol. Endocrinol. 1, 216 (1987)

    Article  Google Scholar 

  52. A. Wells, J. Grahovac, S. Wheeler, B. Ma, D. Lauffenburger, Trends Pharmacol. Sci. 34, 283 (2013)

    Article  Google Scholar 

Download references

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Correspondence to Mingming Wu.

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Geum, D., Kim, B., Chang, A. et al. Epidermal growth factor promotes a mesenchymal over an amoeboid motility of MDA-MB-231 cells embedded within a 3D collagen matrix. Eur. Phys. J. Plus 131, 8 (2016). https://doi.org/10.1140/epjp/i2016-16008-8

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