The use of mixed collagen-Matrigel matrices of increasing complexity recapitulates the biphasic role of cell adhesion in cancer cell migration: ECM sensing, remodeling and forces at the leading edge of cancer invasion
Autoři:
María Anguiano aff001; Xabier Morales aff001; Carlos Castilla aff001; Alejandro Rodríguez Pena aff001; Cristina Ederra aff001; Martín Martínez aff002; Mikel Ariz aff001; Maider Esparza aff001; Hippolyte Amaveda aff003; Mario Mora aff003; Nieves Movilla aff003; José Manuel García Aznar aff003; Iván Cortés-Domínguez aff001; Carlos Ortiz-de-Solorzano aff001
Působiště autorů:
IDISNA, Ciberonc and Solid Tumours and Biomarkers Program, Center for Applied Medical Research, University of Navarra, Pamplona, Spain
aff001; Neuroimaging Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra, Pamplona, Spain
aff002; Department of Mechanical Engineering, Multiscale in Mechanical and Biological Engineering (M2BE), Aragon Institute of Engineering Research (I3A), University of Zaragoza, Zaragoza, Spain
aff003
Vyšlo v časopise:
PLoS ONE 15(1)
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pone.0220019
Souhrn
The migration of cancer cells is highly regulated by the biomechanical properties of their local microenvironment. Using 3D scaffolds of simple composition, several aspects of cancer cell mechanosensing (signal transduction, EMC remodeling, traction forces) have been separately analyzed in the context of cell migration. However, a combined study of these factors in 3D scaffolds that more closely resemble the complex microenvironment of the cancer ECM is still missing. Here, we present a comprehensive, quantitative analysis of the role of cell-ECM interactions in cancer cell migration within a highly physiological environment consisting of mixed Matrigel-collagen hydrogel scaffolds of increasing complexity that mimic the tumor microenvironment at the leading edge of cancer invasion. We quantitatively show that the presence of Matrigel increases hydrogel stiffness, which promotes β1 integrin expression and metalloproteinase activity in H1299 lung cancer cells. Then, we show that ECM remodeling activity causes matrix alignment and compaction that favors higher tractions exerted by the cells. However, these traction forces do not linearly translate into increased motility due to a biphasic role of cell adhesions in cell migration: at low concentration Matrigel promotes migration-effective tractions exerted through a high number of small sized focal adhesions. However, at high Matrigel concentration, traction forces are exerted through fewer, but larger focal adhesions that favor attachment yielding lower cell motility.
Klíčová slova:
Anisotropy – Cancer cell migration – Cell migration – Collagens – Extracellular matrix – Gels – Integrins – Microfluidics
Zdroje
1. Rørth P. Whence Directionality: Guidance Mechanisms in Solitary and Collective Cell Migration. Developmental Cell. 2011. doi: 10.1016/j.devcel.2010.12.014 21238921
2. Chow MT, Luster AD. Chemokines in cancer. Cancer immunology research. 2014. doi: 10.1158/2326-6066.CIR-14-0160 25480554
3. Van Zijl F, Krupitza G, Mikulits W. Initial steps of metastasis: Cell invasion and endothelial transmigration. Mutation Research—Reviews in Mutation Research. 2011. doi: 10.1016/j.mrrev.2011.05.002 21605699
4. Provenzano PP, Inman DR, Eliceiri KW, Trier SM, Keely PJ. Contact guidance mediated three-dimensional cell migration is regulated by Rho/ROCK-dependent matrix reorganization. Biophys J. 2008. doi: 10.1529/biophysj.108.133116 18775961
5. Goetz JG, Minguet S, Navarro-Lérida I, Lazcano JJ, Samaniego R, Calvo E, et al. Biomechanical remodeling of the microenvironment by stromal caveolin-1 favors tumor invasion and metastasis. Cell. 2011. doi: 10.1016/j.cell.2011.05.040 21729786
6. Riching KM, Cox BL, Salick MR, Pehlke C, Riching AS, Ponik SM, et al. 3D collagen alignment limits protrusions to enhance breast cancer cell persistence. Biophys J. 2015. doi: 10.1016/j.bpj.2014.10.035 25468334
7. Ramaswamy S, Ross KN, Lander ES, Golub TR. A molecular signature of metastasis in primary solid tumors. Nat Genet. 2003. doi: 10.1038/ng1060 12469122
8. Levental KR, Yu H, Kass L, Lakins JN, Egeblad M, Erler JT, et al. Matrix Crosslinking Forces Tumor Progression by Enhancing Integrin Signaling. Cell. 2009. doi: 10.1016/j.cell.2009.10.027 19931152
9. Carey SP, Martin KE, Reinhart-King CA. Three-dimensional collagen matrix induces a mechanosensitive invasive epithelial phenotype. Sci Rep. 2017. doi: 10.1038/srep42088 28186196
10. Tsai KKC, Chuang EYY, Little JB, Yuan ZM. Cellular mechanisms for low-dose ionizing radiation-induced perturbation of the breast tissue microenvironment. Cancer Res. 2005. doi: 10.1158/0008-5472.CAN-05-0703 16061655
11. Anguiano M, Castilla C, Maška M, Ederra C, Peláez R, Morales X, et al. Characterization of three-dimensional cancer cell migration in mixed collagen-Matrigel scaffolds using microfluidics and image analysis. PLoS One. 2017. doi: 10.1371/journal.pone.0171417 28166248
12. Geraldo S, Simon A, Vignjevic DM. Revealing the cytoskeletal organization of invasive cancer cells in 3D. J Vis Exp. 2013. doi: 10.3791/50763 24192916
13. Anguiano Salcedo M, Castilla C, Maska M, Ederra C, Fernández Marqués J, Peláez R, et al. Characterization of the role of collagen network structure and composition in cancer cell migration. Conference proceedings:. Annual International Conference of the IEEE Engineering in Medicine and Biology Society IEEE Engineering in Medicine and Biology Society Conference. 2015. pp. 8139–8142. doi: 10.1109/EMBC.2015.7320283
14. Maška M, Ederra C, Fernández-Marqués J, Muñoz-Barrutia A, Kozubek M, Ortiz-De-Solórzano C. Quantification of the 3D collagen network geometry in confocal reflection microscopy. Proceedings—International Conference on Image Processing, ICIP. 2015. doi: 10.1109/ICIP.2015.7351109
15. Stein AM, Vader DA, Jawerth LM, Weitz DA, Sander LM. An algorithm for extracting the network geometry of three-dimensional collagen gels. J Microsc. 2008. doi: 10.1111/j.1365-2818.2008.02141.x 19094023
16. Valero C, Amaveda H, Mora M, García-Aznar JM. Combined experimental and computational characterization of crosslinked collagen-based hydrogels. PLoS One. 2018. doi: 10.1371/journal.pone.0195820 29664953
17. Zuiderveld K. Contrast Limited Adaptive Histogram Equalization. Graphics Gems. 1994. doi: 10.1016/b978-0-12-336156-1.50061–6
18. Maska M, Danek O, Garasa S, Rouzaut A, Munoz-Barrutia A, Ortiz-De-Solorzano C. Segmentation and shape tracking of whole fluorescent cells based on the Chan-Vese model. IEEE Trans Med Imaging. 2013. doi: 10.1109/TMI.2013.2243463 23372077
19. Kiss A, Horvath P, Rothballer A, Kutay U, Csucs G. Nuclear motility in glioma cells reveals a cell-line dependent role of various cytoskeletal components. PLoS One. 2014. doi: 10.1371/journal.pone.0093431 24691067
20. Sander EA, Barocas VH. Comparison of 2D fiber network orientation measurement methods. J Biomed Mater Res—Part A. 2009. doi: 10.1002/jbm.a.31847 18286605
21. Peláez R, Morales X, Salvo E, Garasa S, de Solórzano CO, Martínez A, et al. $β$3 integrin expression is required for invadopodia-mediated ECM degradation in lung carcinoma cells. PLoS One. 2017. doi: 10.1371/journal.pone.0181579 28767724
22. Tsai WH. Moment-preserving thresholding: a new approach. Comput Vision, Graph Image Process. 1985. doi: 10.1016/0734-189x(85)90133-1
23. Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, et al. Fiji: An open-source platform for biological-image analysis. Nature Methods. 2012. doi: 10.1038/nmeth.2019 22743772
24. Horzum U, Ozdil B, Pesen-Okvur D. Step-by-step quantitative analysis of focal adhesions. MethodsX. 2014. doi: 10.1016/j.mex.2014.06.004 26150935
25. Sage D, Neumann FR, Hediger F, Gasser SM, Unser M. Automatic tracking of individual fluorescence particles: Application to the study of chromosome dynamics. IEEE Trans Image Process. 2005. doi: 10.1109/TIP.2005.852787 16190472
26. Legland D, Arganda-Carreras I, Andrey P. MorphoLibJ: Integrated library and plugins for mathematical morphology with ImageJ. Bioinformatics. 2016. doi: 10.1093/bioinformatics/btw413 27412086
27. Steinwachs J, Metzner C, Skodzek K, Lang N, Thievessen I, Mark C, et al. Three-dimensional force microscopy of cells in biopolymer networks. Nat Methods. 2016. doi: 10.1038/nmeth.3685 26641311
28. Motte S, Kaufman LJ. Strain stiffening in collagen i networks. Biopolymers. 2013. doi: 10.1002/bip.22133 23097228
29. Das A, Monteiro M, Barai A, Kumar S, Sen S. MMP proteolytic activity regulates cancer invasiveness by modulating integrins. Sci Rep. 2017. doi: 10.1038/s41598-017-14340-w 29079818
30. Javelaud D, Mauviel A. Crosstalk mechanisms between the mitogen-activated protein kinase pathways and Smad signaling downstream of TGF-$β$: Implications for carcinogenesis. Oncogene. 2005. doi: 10.1038/sj.onc.1208928 16123807
31. Wolf K, Wu YI, Liu Y, Geiger J, Tam E, Overall C, et al. Multi-step pericellular proteolysis controls the transition from individual to collective cancer cell invasion. Nat Cell Biol. 2007. doi: 10.1038/ncb1616 17618273
32. Yeh YC, Ling JY, Chen WC, Lin HH, Tang MJ. Mechanotransduction of matrix stiffness in regulation of focal adhesion size and number: Reciprocal regulation of caveolin-1 and $β$1 integrin. Sci Rep. 2017. doi: 10.1038/s41598-017-14932-6 29118431
33. Discher DE, Janmey P, Wang YL. Tissue cells feel and respond to the stiffness of their substrate. Science. 2005. doi: 10.1126/science.1116995 16293750
34. Gálvez BG, Matías-Román S, Yáñez-Mó M, Sánchez-Madrid F, Arroyo AG. ECM regulates MT1-MMP localization with β1 or αvβ3 integrins at distinct cell compartments modulating its internalization and activity on human endothelial cells. J Cell Biol. 2002. doi: 10.1083/jcb.200205026 12427871
35. Wolf K, Mazo I, Leung H, Engelke K, Von Andrian UH, Deryugina EI, et al. Compensation mechanism in tumor cell migration: Mesenchymal-amoeboid transition after blocking of pericellular proteolysis. J Cell Biol. 2003. doi: 10.1083/jcb.200209006 12527751
36. Humphries JD, Wang P, Streuli C, Geiger B, Humphries MJ, Ballestrem C. Vinculin controls focal adhesion formation by direct interactions with talin and actin. J Cell Biol. 2007. doi: 10.1083/jcb.200703036 18056416
37. Kim DH, Wirtz D. Focal adhesion size uniquely predicts cell migration. FASEB J. 2013. doi: 10.1096/fj.12-220160 23254340
38. Maheshwari G, Brown G, Lauffenburger DA, Wells A, Griffith LG. Cell adhesion and motility depend on nanoscale RGD clustering. J Cell Sci. 2000.
39. Palecek SP, Loftust JC, Ginsberg MH, Lauffenburger DA, Horwitz AF. Integrin-ligand binding properties govern cell migration speed through cell-substratum adhesiveness. Nature. 1997. doi: 10.1038/385537a0 9020360
40. Lee B, Konen J, Wilkinson S, Marcus AI, Jiang Y. Local alignment vectors reveal cancer cell-induced ECM fiber remodeling dynamics. Sci Rep. 2017. doi: 10.1038/srep39498 28045069
41. Sander LM. Modeling contact guidance and invasion by cancer cells. Cancer Research. 2014. doi: 10.1158/0008-5472.CAN-13-3294 25183784
42. Provenzano PP, Eliceiri KW, Campbell JM, Inman DR, White JG, Keely PJ. Collagen reorganization at the tumor-stromal interface facilitates local invasion. BMC Med. 2006. doi: 10.1186/1741-7015-4-38 17190588
43. Goffin JM, Pittet P, Csucs G, Lussi JW, Meister JJ, Hinz B. Focal adhesion size controls tension-dependent recruitment of $α$-smooth muscle actin to stress fibers. J Cell Biol. 2006. doi: 10.1083/jcb.200506179 16401722
44. Malandrino A, Mak M, Kamm RD, Moeendarbary E. Complex mechanics of the heterogeneous extracellular matrix in cancer. Extreme Mechanics Letters. 2018. doi: 10.1016/j.eml.2018.02.003 30135864
45. Harley BA, Freyman TM, Wong MQ, Gibson LJ. A new technique for calculating individual dermal fibroblast contractile forces generated within collagen-GAG scaffolds. Biophys J. 2007. doi: 10.1529/biophysj.106.095471 17586570
46. Reinhart-King CA, Dembo M, Hammer DA. The dynamics and mechanics of endothelial cell spreading. Biophys J. 2005. doi: 10.1529/biophysj.104.054320 15849250
47. Ji L, Lim J, Danuser G. Fluctuations of intracellular forces during cell protrusion. Nat Cell Biol. 2008. doi: 10.1038/ncb1797 19011623
48. Thievessen I, Fakhri N, Steinwachs J, Kraus V, McIsaac RS, Gao L, et al. Vinculin is required for cell polarization, migration, and extracellular matrix remodeling in 3D collagen. FASEB J. 2015. doi: 10.1096/fj.14-268235 26195589
49. Liou YR, Torng W, Kao YC, Sung K Bin, Lee CH, Kuo PL. Substrate stiffness regulates filopodial activities in lung cancer cells. PLoS One. 2014. doi: 10.1371/journal.pone.0089767 24587021
Článek vyšel v časopise
PLOS One
2020 Číslo 1
- Tisícileté topoly, mokří psi, stárnoucí kočky a ospalé octomilky – „jednohubky“ z výzkumu 2024/41
- Jaké jsou aktuální trendy v léčbě karcinomu slinivky?
- Může hubnutí souviset s vyšším rizikem nádorových onemocnění?
- Menstruační krev má značný diagnostický potenciál, mimo jiné u diabetu
- Metamizol jako analgetikum první volby: kdy, pro koho, jak a proč?
Nejčtenější v tomto čísle
- Severity of misophonia symptoms is associated with worse cognitive control when exposed to misophonia trigger sounds
- Chemical analysis of snus products from the United States and northern Europe
- Calcium dobesilate reduces VEGF signaling by interfering with heparan sulfate binding site and protects from vascular complications in diabetic mice
- Effect of Lactobacillus acidophilus D2/CSL (CECT 4529) supplementation in drinking water on chicken crop and caeca microbiome
Zvyšte si kvalifikaci online z pohodlí domova
Všechny kurzy