Adipose tissue fibrosis in human cancer cachexia: the role of TGF beta pathway

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dc.citation.volume17
dc.contributor.authorAlves, Michele Joana
dc.contributor.authorFigueredo, Raquel Galvao
dc.contributor.authorAzevedo, Flavia Figueiredo
dc.contributor.authorCavallaro, Diego Alexandre [UNIFESP]
dc.contributor.authorPinto Neto, Nelson Inacio [UNIFESP]
dc.contributor.authorCarola Lima, Joanna Darck
dc.contributor.authorMatos-Neto, Emidio
dc.contributor.authorRadloff, Katrin
dc.contributor.authorRiccardi, Daniela Mendes
dc.contributor.authorCamargo, Rodolfo Gonzalez
dc.contributor.authorMartins De Alcantara, Paulo Sergio
dc.contributor.authorOtoch, Jose Pinhata
dc.contributor.authorBatista Junior, Miguel Luiz
dc.contributor.authorSeelaender, Marilia
dc.coverageLondon
dc.date.accessioned2020-07-17T14:02:39Z
dc.date.available2020-07-17T14:02:39Z
dc.date.issued2017
dc.description.abstractBackground: Cancer cachexia is a multifactorial syndrome that dramatically decreases survival. Loss of white adipose tissue (WAT) is one of the key characteristics of cachexia. WAT wasting is paralleled by microarchitectural remodeling in cachectic cancer patients. Fibrosis results from uncontrolled ECM synthesis, a process in which, transforming growth factor-beta (TGF beta) plays a pivotal role. So far, the mechanisms involved in adipose tissue (AT) re-arrangement, and the role of TGF beta in inducing AT remodeling in weight-losing cancer patients are poorly understood. This study examined the modulation of ECM components mediated by TGF beta pathway in fibrotic AT obtained from cachectic gastrointestinal cancer patients. Methods: After signing the informed consent form, patients were enrolled into the following groups: cancer cachexia (CC, n = 21), weight-stable cancer (WSC, n = 17), and control (n = 21). The total amount of collagen and elastic fibers in the subcutaneous AT was assessed by histological analysis and by immunohistochemistry. TGF beta isoforms expression was analyzed by Multiplex assay and by immunohistochemistry. Alpha-smooth muscle actin (aSMA), fibroblast-specific protein (FSP1), Smad3 and 4 were quantified by qPCR and/or by immunohistochemistry. Interleukin (IL) 2, IL5, IL8, IL13 and IL17 content, cytokines known to be associated with fibrosis, was measured by Multiplex assay. Results: There was an accumulation of collagen and elastic fibers in the AT of CC, as compared with WSC and controls. Collagens type I, III, VI, and fibronectin expression was enhanced in the tissue of CC, compared with both WSC and control. The pronounced expression of aSMA in the surrounding of adipocytes, and the increased mRNA content for FSP1 (20-fold) indicate the presence of activated myofibroblastsen
dc.description.abstractparticularly in CC. TGF beta 1 and TGF beta 3 levels were up-regulated by cachexia in AT, as well in the isolated adipocytes. Smad3 and Smad4 labeling was found to be more evident in the fibrotic areas of CC adipose tissue. Conclusions: Cancer cachexia promotes the development of AT fibrosis, in association with altered TGF beta signaling, compromising AT organization and function.en
dc.description.affiliationUniv Sao Paulo, Inst Biomed Sci, Canc Metab Res Grp, Sao Paulo, Brazil
dc.description.affiliationUniv Sao Paulo, Fac Med, Dept Surg, Sao Paulo, Brazil
dc.description.affiliationUniv Sao Paulo, Univ Hosp, Dept Clin Surg, Sao Paulo, Brazil
dc.description.affiliationUniv Mogi das Cruzes, Biotechnol Grp, Lab Adipose Tissue Biol, Mogi Das Cruzes, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Nutr, Sao Paulo, Brazil
dc.description.affiliationUniv Estadual Campinas, Fac Nursing, Campinas, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Nutr, Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipSao Paulo Research Foundation (FAPESP)
dc.description.sponsorshipCAPES
dc.description.sponsorshipIDFAPESP: 2012/50079-0
dc.format.extent-
dc.identifierhttp://dx.doi.org/10.1186/s12885-017-3178-8
dc.identifier.citationBmc Cancer. London, v. 17, p. -, 2017.
dc.identifier.doi10.1186/s12885-017-3178-8
dc.identifier.fileWOS000397775800004.pdf
dc.identifier.issn1471-2407
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/54928
dc.identifier.wosWOS:000397775800004
dc.language.isoeng
dc.publisherBiomed Central Ltd
dc.relation.ispartofBmc Cancer
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectCancer cachexiaen
dc.subjectFibrosisen
dc.subjectAdipose tissueen
dc.subjectExtracellular matrixen
dc.subjectTGF betaen
dc.titleAdipose tissue fibrosis in human cancer cachexia: the role of TGF beta pathwayen
dc.typeinfo:eu-repo/semantics/article
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