Soft Fibrin Gels Promote Selection and Growth of Tumorigenic Cells

Overview

Journal Nat Mater

Date 2012 Jul 4

PMID 22751180

Citations 199

Authors

Jing Liu

Youhua Tan

Huafeng Zhang

Yi Zhang

Pingwei Xu

Junwei Chen

Yeh-Chuin Poh

Ke Tang

Ning Wang

Bo Huang

Affiliations

Soon will be listed here.

Abstract

The identification of stem-cell-like cancer cells through conventional methods that depend on stem cell markers is often unreliable. We developed a mechanical method for selecting tumorigenic cells by culturing single cancer cells in fibrin matrices of ~100 Pa in stiffness. When cultured within these gels, primary human cancer cells or single cancer cells from mouse or human cancer cell lines grew within a few days into individual round colonies that resembled embryonic stem cell colonies. Subcutaneous or intravenous injection of 10 or 100 fibrin-cultured cells in syngeneic or severe combined immunodeficiency mice led to the formation of solid tumours at the site of injection or at the distant lung organ much more efficiently than control cancer cells selected using conventional surface marker methods or cultured on conventional rigid dishes or on soft gels. Remarkably, as few as ten such cells were able to survive and form tumours in the lungs of wild-type non-syngeneic mice.

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References

Levental K, Yu H, Kass L, Lakins J, Egeblad M, Erler J . Matrix crosslinking forces tumor progression by enhancing integrin signaling. Cell. 2009; 139(5):891-906. PMC: 2788004. DOI: 10.1016/j.cell.2009.10.027. View

Palumbo J, Degen J . Fibrinogen and tumor cell metastasis. Haemostasis. 2002; 31 Suppl 1:11-5. View

Poh Y, Chowdhury F, Tanaka T, Wang N . Embryonic stem cells do not stiffen on rigid substrates. Biophys J. 2010; 99(2):L19-21. PMC: 2905070. DOI: 10.1016/j.bpj.2010.04.057. View

Wirtz D, Konstantopoulos K, Searson P . The physics of cancer: the role of physical interactions and mechanical forces in metastasis. Nat Rev Cancer. 2011; 11(7):512-22. PMC: 3262453. DOI: 10.1038/nrc3080. View

Gupta P, Fillmore C, Jiang G, Shapira S, Tao K, Kuperwasser C . Stochastic state transitions give rise to phenotypic equilibrium in populations of cancer cells. Cell. 2011; 146(4):633-44. DOI: 10.1016/j.cell.2011.07.026. View

Hiyama E, Hiyama K . Telomere and telomerase in stem cells. Br J Cancer. 2007; 96(7):1020-4. PMC: 2360127. DOI: 10.1038/sj.bjc.6603671. View

van Sluis G, Bruggemann L, Esmon C, Kamphuisen P, Richel D, Buller H . Endogenous activated protein C is essential for immune-mediated cancer cell elimination from the circulation. Cancer Lett. 2011; 306(1):106-10. PMC: 3159049. DOI: 10.1016/j.canlet.2011.02.038. View

Chowdhury F, Na S, Li D, Poh Y, Tanaka T, Wang F . Material properties of the cell dictate stress-induced spreading and differentiation in embryonic stem cells. Nat Mater. 2009; 9(1):82-8. PMC: 2833279. DOI: 10.1038/nmat2563. View

Quintana E, Shackleton M, Sabel M, Fullen D, Johnson T, Morrison S . Efficient tumour formation by single human melanoma cells. Nature. 2008; 456(7222):593-8. PMC: 2597380. DOI: 10.1038/nature07567. View

10.

Cordenonsi M, Zanconato F, Azzolin L, Forcato M, Rosato A, Frasson C . The Hippo transducer TAZ confers cancer stem cell-related traits on breast cancer cells. Cell. 2011; 147(4):759-72. DOI: 10.1016/j.cell.2011.09.048. View

11.

Pathak A, Kumar S . Biophysical regulation of tumor cell invasion: moving beyond matrix stiffness. Integr Biol (Camb). 2011; 3(4):267-78. DOI: 10.1039/c0ib00095g. View

12.

Dieter S, Ball C, Hoffmann C, Nowrouzi A, Herbst F, Zavidij O . Distinct types of tumor-initiating cells form human colon cancer tumors and metastases. Cell Stem Cell. 2011; 9(4):357-65. DOI: 10.1016/j.stem.2011.08.010. View

13.

Ju Y, Janmey P, McCormick M, Sawyer E, Flanagan L . Enhanced neurite growth from mammalian neurons in three-dimensional salmon fibrin gels. Biomaterials. 2007; 28(12):2097-108. PMC: 1991290. DOI: 10.1016/j.biomaterials.2007.01.008. View

14.

Uibo R, Laidmae I, Sawyer E, Flanagan L, Georges P, Winer J . Soft materials to treat central nervous system injuries: evaluation of the suitability of non-mammalian fibrin gels. Biochim Biophys Acta. 2009; 1793(5):924-30. PMC: 2895977. DOI: 10.1016/j.bbamcr.2009.01.007. View

15.

Gupta P, Chaffer C, Weinberg R . Cancer stem cells: mirage or reality?. Nat Med. 2009; 15(9):1010-2. DOI: 10.1038/nm0909-1010. View

16.

Dupont S, Morsut L, Aragona M, Enzo E, Giulitti S, Cordenonsi M . Role of YAP/TAZ in mechanotransduction. Nature. 2011; 474(7350):179-83. DOI: 10.1038/nature10137. View

17.

Senger D, Perruzzi C, Streit M, Koteliansky V, de Fougerolles A, Detmar M . The alpha(1)beta(1) and alpha(2)beta(1) integrins provide critical support for vascular endothelial growth factor signaling, endothelial cell migration, and tumor angiogenesis. Am J Pathol. 2002; 160(1):195-204. PMC: 1867136. DOI: 10.1016/s0002-9440(10)64363-5. View

18.

Bonnet D, Dick J . Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med. 1997; 3(7):730-7. DOI: 10.1038/nm0797-730. View

19.

Gilbert P, Havenstrite K, Magnusson K, Sacco A, Leonardi N, Kraft P . Substrate elasticity regulates skeletal muscle stem cell self-renewal in culture. Science. 2010; 329(5995):1078-81. PMC: 2929271. DOI: 10.1126/science.1191035. View

20.

Valastyan S, Weinberg R . Tumor metastasis: molecular insights and evolving paradigms. Cell. 2011; 147(2):275-92. PMC: 3261217. DOI: 10.1016/j.cell.2011.09.024. View