000074911 001__ 74911
000074911 005__ 20200117221635.0
000074911 0247_ $$2doi$$a10.1038/s41598-018-30683-4
000074911 0248_ $$2sideral$$a107493
000074911 037__ $$aART-2018-107493
000074911 041__ $$aeng
000074911 100__ $$0(orcid)0000-0002-4220-105X$$aPlou, J.
000074911 245__ $$aFrom individual to collective 3D cancer dissemination: roles of collagen concentration and TGF-ß
000074911 260__ $$c2018
000074911 5060_ $$aAccess copy available to the general public$$fUnrestricted
000074911 5203_ $$aCancer cells have the ability to migrate from the primary (original) site to other places in the body. The extracellular matrix affects cancer cell migratory capacity and has been correlated with tissue-specific spreading patterns. However, how the matrix orchestrates these behaviors remains unclear. Here, we investigated how both higher collagen concentrations and TGF-ß regulate the formation of H1299 cell (a non-small cell lung cancer cell line) spheroids within 3D collagen-based matrices and promote cancer cell invasive capacity. We show that at low collagen concentrations, tumor cells move individually and have moderate invasive capacity, whereas when the collagen concentration is increased, the formation of cell clusters is promoted. In addition, when the concentration of TGF-ß in the microenvironment is lower, most of the clusters are aggregates of cancer cells with a spheroid-like morphology and poor migratory capacity. In contrast, higher concentrations of TGF-ß induced the formation of clusters with a notably higher invasive capacity, resulting in clear strand-like collective cell migration. Our results show that the concentration of the extracellular matrix is a key regulator of the formation of tumor clusters that affects their development and growth. In addition, chemical factors create a microenvironment that promotes the transformation of idle tumor clusters into very active, invasive tumor structures. These results collectively demonstrate the relevant regulatory role of the mechano-chemical microenvironment in leading the preferential metastasis of tumor cells to specific tissues with high collagen concentrations and TFG-ß activity.
000074911 536__ $$9This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 737543-IMAGO$$9info:eu-repo/grantAgreement/EC/H2020/737543/EU/Image Analysis Online Services for in-vitro experiments/IMAGO$$9info:eu-repo/grantAgreement/EC/FP7/306571/EU/Predictive modelling and simulation in mechano-chemo-biology: a computer multi-approach/INSILICO-CELL$$9info:eu-repo/grantAgreement/ES/MINECO/DPI2015-64221-C2-1-R
000074911 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000074911 590__ $$a4.011$$b2018
000074911 591__ $$aMULTIDISCIPLINARY SCIENCES$$b14 / 69 = 0.203$$c2018$$dQ1$$eT1
000074911 592__ $$a1.414$$b2018
000074911 593__ $$aMultidisciplinary$$c2018$$dQ1
000074911 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000074911 700__ $$0(orcid)0000-0003-2237-8859$$aJuste-Lanas, Y.$$uUniversidad de Zaragoza
000074911 700__ $$aOlivares, V.$$uUniversidad de Zaragoza
000074911 700__ $$0(orcid)0000-0002-3796-4482$$adel Amo, C.$$uUniversidad de Zaragoza
000074911 700__ $$0(orcid)0000-0002-3784-1140$$aBorau, C.$$uUniversidad de Zaragoza
000074911 700__ $$0(orcid)0000-0002-9864-7683$$aGarcía-Aznar, J.M.$$uUniversidad de Zaragoza
000074911 7102_ $$11002$$2050$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Biología Celular
000074911 7102_ $$15004$$2605$$aUniversidad de Zaragoza$$bDpto. Ingeniería Mecánica$$cÁrea Mec.Med.Cont. y Teor.Est.
000074911 773__ $$g8, 1 (2018), 12723 [14 pp]$$pSci. rep.$$tSCIENTIFIC REPORTS$$x2045-2322
000074911 8564_ $$s5716940$$uhttps://zaguan.unizar.es/record/74911/files/texto_completo.pdf$$yVersión publicada
000074911 8564_ $$s114095$$uhttps://zaguan.unizar.es/record/74911/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000074911 909CO $$ooai:zaguan.unizar.es:74911$$particulos$$pdriver
000074911 951__ $$a2020-01-17-22:01:58
000074911 980__ $$aARTICLE