Colorectal cancer desmoplastic reaction up-regulates collagen synthesis and restricts cancer cell invasion

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dc.contributor.author Coulson-Thomas, Vivien Jane [UNIFESP]
dc.contributor.author Coulson-Thomas, Yvette May [UNIFESP]
dc.contributor.author Gesteira, Tarsis F. [UNIFESP]
dc.contributor.author Paula, Claudia A. A. de [UNIFESP]
dc.contributor.author Mader, Ana M.
dc.contributor.author Waisberg, Jaques
dc.contributor.author Pinhal, Maria A. [UNIFESP]
dc.contributor.author Friedl, Andreas
dc.contributor.author Toma, Leny [UNIFESP]
dc.contributor.author Nader, Helena B. [UNIFESP]
dc.date.accessioned 2016-01-24T14:17:23Z
dc.date.available 2016-01-24T14:17:23Z
dc.date.issued 2011-11-01
dc.identifier http://dx.doi.org/10.1007/s00441-011-1254-y
dc.identifier.citation Cell and Tissue Research. New York: Springer, v. 346, n. 2, p. 223-236, 2011.
dc.identifier.issn 0302-766X
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/34182
dc.description.abstract During cancer cell growth many tumors exhibit various grades of desmoplasia, unorganized production of fibrous or connective tissue, composed mainly of collagen fibers and myofibroblasts. the accumulation of an extracellular matrix (ECM) surrounding tumors directly affects cancer cell proliferation, migration and spread; therefore the study of desmoplasia is of vital importance. Stromal fibroblasts surrounding tumors are activated to myofibroblasts and become the primary producers of ECM during desmoplasia. the composition, density and organization of this ECM accumulation play a major role on the influence desmoplasia has upon tumor cells. in this study, we analyzed desmoplasia in vivo in human colorectal carcinoma tissue, detecting an up-regulation of collagen I, collagen IV and collagen V in human colorectal cancer desmoplastic reaction. These components were then analyzed in vitro co-cultivating colorectal cancer cells (Caco-2 and HCT116) and fibroblasts utilizing various co-culture techniques. Our findings demonstrate that direct cell-cell contact between fibroblasts and colorectal cancer cells evokes an increase in ECM density, composed of unorganized collagens (I, III, IV and V) and proteoglycans (biglycan, fibromodulin, perlecan and versican). the desmoplastic collagen fibers were thick, with an altered orientation, as well as deposited as bundles. This increased ECM density inhibited the migration and invasion of the colorectal tumor cells in both 2D and 3D co-culture systems. Therefore this study sheds light on a possible restricting role desmoplasia could play in colorectal cancer invasion. en
dc.description.sponsorship Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorship Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorship Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.format.extent 223-236
dc.language.iso eng
dc.publisher Springer
dc.relation.ispartof Cell and Tissue Research
dc.rights Acesso restrito
dc.subject Myofibroblasts en
dc.subject Stromal reaction en
dc.subject Proteoglycans en
dc.subject Collagen en
dc.subject 2D-and 3D-cultures en
dc.title Colorectal cancer desmoplastic reaction up-regulates collagen synthesis and restricts cancer cell invasion en
dc.type Artigo
dc.rights.license http://www.springer.com/open+access/authors+rights?SGWID=0-176704-12-683201-0
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.contributor.institution Fac Med ABC
dc.contributor.institution Univ Wisconsin
dc.description.affiliation Universidade Federal de São Paulo, Dept Bioquim, Escola Paulista Med, BR-04044020 São Paulo, Brazil
dc.description.affiliation Universidade Federal de São Paulo, Dept Biochem, BR-04044020 São Paulo, Brazil
dc.description.affiliation Fac Med ABC, Dept Pathol, Santo Andre, SP, Brazil
dc.description.affiliation Fac Med ABC, Dept Gastrosurg, Santo Andre, SP, Brazil
dc.description.affiliation Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53792 USA
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Dept Bioquim, Escola Paulista Med, BR-04044020 São Paulo, Brazil
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Dept Biochem, BR-04044020 São Paulo, Brazil
dc.description.sponsorshipID FAPESP: 2007/59801-1
dc.identifier.doi 10.1007/s00441-011-1254-y
dc.description.source Web of Science
dc.identifier.wos WOS:000297122600008



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