Abstract
Growth factor-induced chemotaxis of cancer cells is believed to play a critical role in metastasis, directing the spread of cancer from the primary tumor to secondary sites in the body. Understanding the mechanistic and quantitative behavior of cancer cell migration in growth factor gradients would greatly help in future treatment of metastatic cancers. Using a novel microfluidic chemotaxis chamber capable of simultaneously generating multiple growth factor gradients, we examined the migration of the human metastatic breast cancer cell line MDA-MB-231 in various conditions. First, we quantified and compared the migration in two gradients of epidermal growth factor (EGF) spanning different concentrations: 0–50 ng/ml and 0.1–6 ng/ml. Cells showed a stronger response in the 0–50 ng/ml gradient. However, the fact that even a shallow gradient of EGF can induce chemotaxis, and that EGF can direct migration over a large dynamic range of gradients, confirms the potency of EGF as a chemoattractant. Second, we investigated the effect of antibody against the EGF receptor (EGFR) on MDA-MB-231 chemotaxis. Quantitative analysis indicated that anti-EGFR antibody impaired both motility and directional orientation (CI = 0.03, speed = 0.71 μm/min), indicating that cell motility was induced by the activation of EGFR. The ability to compare, in terms of quantitative parameters, the effects of different pharmaceutical inhibitors, as well as subtle differences in experimental conditions, will aid in our understanding of mechanisms that drive metastasis. The microfluidic chamber described in this work will provide a platform for cell-based assays that can be used to compare the effectiveness of different pharmaceutical compounds targeting cell migration and metastasis.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
M. Bailly, L. Yan, G.M. Whitesides, J.S. Condeelis and J.E. Segall, Experimental Cell Research 241, 285–299 (1998).
C.G. Bredin, Z. Liu, D. Hauzenberger and J. Klominek, Int J Cancer 82, 338–45 (1999).
A.F. Chambers, A.C. Groom and I.C. MacDonald, Nat Rev Cancer 2, 563–72 (2002).
F. Ciardiello and G. Tortora, Clin Cancer Res 7, 2958–2970 (2001).
J.S. Condeelis, J.B. Wyckoff, M. Bailly, R. Pestell, D. Lawrence, J. Backer and J.E. Segall, Semin Cancer Biol 11, 119–8 (2001).
S.K.W. Dertinger, D.T. Chiu, N.L. Jeon and G.M. Whitesides, Anal Chem 73, 1240–1246 (2001).
S. Dluz, S. Higashiyama, D. Damm, J. Abraham and M. Klagsbrun, J Biol Chem 268, 18330–18334 (1993).
O.M. Fischer, S. Streit, S. Hart and A. Ullrich, Current Opinion in Chemical Biology 7, 490–495 (2003).
N.L. Jeon, H. Baskaran, S.K.W. Dertinger, G.M. Whitesides, L. Van De Water and M. Toner, Nat Biotechnol 20 826–830 (2002).
N.L. Jeon, S.K.W. Dertinger, D.T. Chiu and G.M. Whitesides, Langmuir 16, 8311–8316 (2000).
J. Kassis, D.A. Lauffenburger, T. Turner and A. Wells, Seminars in Cancer Biology 11, 105–119 (2001).
N. Kume and M.J. Gimbrone, J Clin Invest 93, 907–11 (1994).
M.D. Levine, L.A. Liotta and M.L. Stracke, EXS 74, 157–179 (1995).
F. Lin, W. Saadi, S.W. Rhee, S.-J. Wang, S. Mittal and N.L. Jeon, Lab Chip 4, DOI: 10.1039/b313600k (2004).
G. Maheshwari, A. Wells, L.G. Griffith and D.A. Lauffenburger, Biophys J 76, 2814–23 (1999).
J. Mendelsohn, Endocr Relat Cancer 8, 3–9 (2001).
J. Mendelsohn and J. Baselga, Oncogene 19, 6550–65 (2000).
G. Peoples, S. Blotnick, K. Takahashi, M. Freeman, M. Klagsbrun and T. Eberlein, PNAS 92, 6547–6551 (1995).
J.T. Price, T. Tiganis, A. Agarwal, D. Djakiew and E.W. Thompson, Cancer Research 59, 5475–5478 (1999).
R. Radinsky, S. Risin, D. Fan, Z. Dong, D. Bielenberg, C. Bucana and I.J. Fidler, Clin Cancer Res 1, 19–31 (1995).
P.S. Steeg, Nat Rev Cancer 3, 55–63 (2003).
H. Steven Wiley, S.Y. Shvartsman and D.A. Lauffenburger, Trends in Cell Biology 13, 43-50 (2003).
T. Turner, M.V. Epps-Fung, J. Kassis and A. Wells, Clin Cancer Res 3, 2275–82 (1997).
S.-J. Wang, W. Saadi, F. Lin, C.M.-C. Nguyen and N.L. Jeon, Exp Cell Res 300, 180–189 (2004).
A. Wells, Adv Cancer Res 78, 31–101 (2000).
A. Wells, J. Kassis, J. Solava, T. Turner and D.A. Lauffenburger, Acta Oncol 41, 124–30 (2002).
G.M. Whitesides, E. Ostuni, S. Takayama, X. Jiang and D.E. Ingber, Annu Rev Biomed Eng 3, 335–73 (2001).
P.C. Wilkinson, Journal of Immunological Methods 216, 139–153 (1998).
J. Woodburn, Pharmacol Ther 82, 241–50 (1999).
J.B. Wyckoff, L. Insel, K. Khazaie, R.B. Lichtner, J.S. Condeelis and J.E. Segall, Experimental Cell Research 242, 100–109 (1998).
J.B. Wyckoff, J.G. Jones, J.S. Condeelis and J.E. Segall, Cancer Res 60, 2504–2511 (2000).
J.B. Wyckoff, J.E. Segall and J.S. Condeelis, Cancer Res 60, 5401–4 (2000).
X. Yang, J. Corvalan, P. Wang, C. Roy and C. Davis, J Leukoc Biol 66, 401–410 (1999).
J.H. Zar, Biostatistical Analysis (Prentice-Hall, Inc, Upper Saddle River, New Jersey, (1996)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Saadi, W., Wang, SJ., Lin, F. et al. A parallel-gradient microfluidic chamber for quantitative analysis of breast cancer cell chemotaxis. Biomed Microdevices 8, 109–118 (2006). https://doi.org/10.1007/s10544-006-7706-6
Issue Date:
DOI: https://doi.org/10.1007/s10544-006-7706-6