Citation: Yuan Tianying, Gao Dan, Li Shangfu, Jiang Yuyang. Co-culture of tumor spheroids and monocytes in a collagen matrix-embedded microfluidic device to study the migration of breast cancer cells[J]. Chinese Chemical Letters, ;2019, 30(2): 331-336. doi: 10.1016/j.cclet.2018.07.013 shu

Co-culture of tumor spheroids and monocytes in a collagen matrix-embedded microfluidic device to study the migration of breast cancer cells

Yuan Tianying ^a,b ,
Gao Dan ^a,b,*, ,
Li Shangfu ^a,b ,
Jiang Yuyang ^a,c

a.
State Key Laboratory of Chemical Oncogenomics, The Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, China
b.
Key Laboratory of Metabolomics at Shenzhen, Shenzhen 518055, China
c.
School of Medicine, Tsinghua University, Beijing 100084, China

gao.dan@sz.tsinghua.edu.cn

Received Date: 22 June 2018
Revised Date: 17 July 2018
Accepted Date: 18 July 2018
Available Online: 21 February 2018

Figures(4)

Recapitulating the tumor microenvironment is a major challenge in the development of in vitro tumor model for the study of cancer biology and therapeutic treatments. 3D multicellular tumor spheroids (MCTS) have been used as reliable models of mimicking in vivo solid tumors. Macrophages and extracellular matrix (ECM), regarded as two key factors of the tumor microenvironment, play significant roles in tumor progression and drug resistance. In order to investigate their effects on tumor cell migration, a microfluidic chip-based 3D breast cancer model was developed by co-culturing monodisperse MCTS with monocytes in 3D collagen matrix. A reversible bonding technique was employed for the fabrication of the microfluidic chip, which made it easier for MCTS formation and tailoring the MCTS co-culture conditions. When co-culturing monocytes with low invasive T47D spheroids or high invasive MD-MBA-231 spheroids, we found that T47D cells with the stimulation of macrophage colony-stimulating factor (M-CSF) and MD-MBA-231 cells could polarize monocytes into tumor-associated macrophages (TAMs). The increased stiffness via increasing collagen concentration decreased tumor cell migration, whereas the presence of TAMs enhanced the migration ability of cells. Moreover, M-CSF-activated TAMs promoted the migration of T47D tumor cells via the regulation of TGFβ1. Overall, this 3D co-culture microfluidic model may be useful for studying tumor progress and may offer a reliable and low-cost method for evaluation of drug efficiency.
- Tumor microenvironment,
- Multicellular tumor spheroids,
- Tumor-associated macrophages,
- Extracellular matrix stiffness,
- Microfluidics
1. [1]
  N. Harbeck, M. Gnant, Lancet 389(2017) 1134-1150. doi: 10.1016/S0140-6736(16)31891-8
2. [2]
  S. Nath, G.R. Devi, Pharmacol. Ther. 163(2016) 94-108. doi: 10.1016/j.pharmthera.2016.03.013
3. [3]
  K.M. Tevis, Y.L. Colson, M.W. Grinstaff, Adv. Biosys. 1(2017) 1700083. doi: 10.1002/adbi.v1.10
4. [4]
  T. Hagemann, S.C. Robinson, M. Schulz, L. Trumper, et al., Carcinogenesis 25(2004) 1543-1549. doi: 10.1093/carcin/bgh146
5. [5]
  T. Hagemann, J. Wilson, H. Kulbe, et al., J. Immunol. 175(2005) 1197-1205. doi: 10.4049/jimmunol.175.2.1197
6. [6]
  S. Joshi, A.R. Singh, M. Zulcic, et al., Mol. Cancer Res. 12(2014) 1520-1531. doi: 10.1158/1541-7786.MCR-13-0682
7. [7]
  K. Vinnakota, Y. Zhang, B.C. Selvanesan, et al., J. Cell. Physiol. 232(2017) 3468-3480. doi: 10.1002/jcp.v232.12
8. [8]
  X. Zhao, J. Qu, Y. Sun, et al., Oncotarget 8(2017) 30576-30586.
9. [9]
  P. Lu, V.M. Weaver, Z. Werb, J. Cell Biol. 196(2012) 395-406. doi: 10.1083/jcb.201102147
10. [10]
  F. Spill, D.S. Reynolds, R.D. Kamm, et al., Curr. Opin. Biotechnol. 40(2016) 41-48.
11. [11]
  F. Kai, H. Laklai, V.M. Weaver, Trends Cell Biol. 26(2016) 486-497. doi: 10.1016/j.tcb.2016.03.007
12. [12]
  M. Plodinec, M. Loparic, C.A. Monnier, et al., Nat. Nanotechnol. 7(2012) 757-765. doi: 10.1038/nnano.2012.167
13. [13]
  S. Su, Q. Liu, J. Chen, et al., Cancer cell 25(2014) 605-620. doi: 10.1016/j.ccr.2014.03.021
14. [14]
  K. Jin, N.B. Pandey, A.S. Popel, Oncotarget 8(2017) 60210-60222.
15. [15]
  E. Cukierman, R. Pankov, D.R. Stevens, et al., Science 294(2001) 1708-1712. doi: 10.1126/science.1064829
16. [16]
  S. Ma, J. Zhou, Y. Zhang, et al., ACS Appl. Mater. Interfaces 8(2016) 28468-28479. doi: 10.1021/acsami.6b09633
17. [17]
  L. Gutzweiler, S. Kartmann, K. Troendle, et al., Biofabrication 9(2017) 025027-025037. doi: 10.1088/1758-5090/aa7218
18. [18]
  S. Breslin, L. O'Driscoll, Drug Discov. Today 18(2013) 240-249. doi: 10.1016/j.drudis.2012.10.003
19. [19]
  G. Lazzari, P. Couvreur, S. Mura, Polym. Chem. 8(2017) 4947-4969. doi: 10.1039/C7PY00559H
20. [20]
  Z. He, W. Zhang, S. Mao, et al., Anal. Chem. 90(2018) 5540-5545. doi: 10.1021/acs.analchem.8b00755
21. [21]
  M. Jie, S. Mao, H. Li, et al., Chin. Chem. Lett. 28(2017) 1625-1630. doi: 10.1016/j.cclet.2017.05.024
22. [22]
  L. Lin, X. Lin, L. Lin, et al., Anal. Chem. 89(2017) 10037-10044. doi: 10.1021/acs.analchem.7b02593
23. [23]
  R. Li, J.D. Hebert, T.A. Lee, et al., Cancer Res. 77(2017) 279-290. doi: 10.1158/0008-5472.CAN-16-0442
24. [24]
  J. Bai, G. Adriani, T.M. Dang, et al., Oncotarget 6(2015) 25295-25307.
25. [25]
  J.H. Lee, S.K. Kim, I.A. Khawar, et al., J. Exp. Clin. Cancer Res. 37(2018) 4-15. doi: 10.1186/s13046-017-0654-6
26. [26]
  M. Serra, I. Pereiro, A. Yamada, et al., Lab Chip 17(2017) 629-634. doi: 10.1039/C6LC01319H
27. [27]
  A. Zuchowska, E. Jastrzebska, M. Chudy, et al., Anal. Chim. Acta 990(2017) 110-120. doi: 10.1016/j.aca.2017.07.009
28. [28]
  D.M. Richards, J. Hettinger, M. Feuerer, Cancer Microenviron. 6(2013) 179-191. doi: 10.1007/s12307-012-0123-x
29. [29]
  F. Geissmann, M.G. Manz, S. Jung, M.H. Sieweke, et al., Science 327(2010) 656-661. doi: 10.1126/science.1178331
30. [30]
  Y. Komohara, M. Jinushi, M. Takeya, Cancer Sci. 105(2014) 1-8. doi: 10.1111/cas.12314
31. [31]
  P. Jeannin, L. Paolini, C. Adam, et al., FEBS J. 285(2018) 680-699. doi: 10.1111/febs.2018.285.issue-4
32. [32]
  E. van Overmeire, B. Stijlemans, F. Heymann, et al., Cancer Res. 76(2016) 35-42.
33. [33]
  M. Miron-Mendoza, J. Seemann, F. Grinnell, Biomaterials 31(2010) 6425-6435. doi: 10.1016/j.biomaterials.2010.04.064
34. [34]
  J. Steinwachs, C. Metzner, K. Skodzek, et al., Nat. Methods 13(2016) 171-176. doi: 10.1038/nmeth.3685
35. [35]
  H. Ahmadzadeh, M.R. Webster, R. Behera, et al., Proc. Natl. Acad. Sci. U. S. A. 114(2017) E1617-E1626. doi: 10.1073/pnas.1617037114
36. [36]
  T. Lecuit, A.S. Yap, Nat. Cell Biol. 17(2015) 533-539. doi: 10.1038/ncb3136
37. [37]
  M. Canel, A. Serrels, M.C. Frame, et al., J. Cell Sci. 126(2013) 393-401. doi: 10.1242/jcs.100115
38. [38]
  J.F. Zhao, C. Klausen, X. Qiu, et al., Oncotarget 7(2016) 28881-28890.
39. [39]
  J. Massague, Cell 134(2008) 215-230. doi: 10.1016/j.cell.2008.07.001
40. [40]
  H.Y. Chong, Y. Vodovotz, G.W. Cox, et al., J. Cell. Physiol. 178(1999) 275-283.
41. [41]
  X.Z. Ye, S.L. Xu, Y.H. Xin, et al., J. Immunol. 189(2012) 444-453. doi: 10.4049/jimmunol.1103248
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