Interface between breast cancer cells and the tumor microenvironment using platelet-rich plasma to promote tumor angiogenesis - influence of platelets and fibrin bundles on the behavior of breast tumor cells

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dc.citation.issue10
dc.citation.volume8
dc.contributor.authorAndrade, Sheila Siqueira [UNIFESP]
dc.contributor.authorSumikawa, Joana Tomomi [UNIFESP]
dc.contributor.authorCastro, Eloisa Dognani [UNIFESP]
dc.contributor.authorBatista, Fabricio Pereira [UNIFESP]
dc.contributor.authorParedes-Gamero, Edgar [UNIFESP]
dc.contributor.authorOliveira, Lilian Carolina
dc.contributor.authorGuerra, Izabel Monasterio [UNIFESP]
dc.contributor.authorPeres, Giovani Bravin [UNIFESP]
dc.contributor.authorCavalheiro, Renan Pelluzzi [UNIFESP]
dc.contributor.authorJuliano, Luiz
dc.contributor.authorNazario, Afonso Pinto [UNIFESP]
dc.contributor.authorFacina, Gil [UNIFESP]
dc.contributor.authorTsai, Siu Mui
dc.contributor.authorVilela Oliva, Maria Luiza [UNIFESP]
dc.contributor.authorBatista Castello Girao, Manoel Joao [UNIFESP]
dc.coverageOrchard Park
dc.date.accessioned2020-07-17T14:02:40Z
dc.date.available2020-07-17T14:02:40Z
dc.date.issued2017
dc.description.abstractCancer progression is associated with an evolving tissue interface of direct epithelial-tumor microenvironment interactions. In biopsies of human breast tumors, extensive alterations in molecular pathways are correlated with cancer staging on both sides of the tumor-stroma interface. These interactions provide a pivotal paracrine signaling to induce malignant phenotype transition, the epithelial-mesenchymal transition (EMT). We explored how the direct contact between platelets-fibrin bundles primes metastasis using platelet-rich plasma (PRP) as a source of growth factors and mimics the provisional fibrin matrix between actively growing breast cancer cells and the tumor stroma. We have demonstrated PRP functions, modulating cell proliferation that is tumor-subtype and cancer cell-type-specific. Epithelial and stromal primary cells were prepared from breast cancer biopsies from 21 women with different cancer subtypes. Cells supplemented with PRP were immunoblotted with anti-phospho and total Src-Tyr-416, FAK-Try-925, E-cadherin, N-cadherin, TGF-beta, Smad2, and Snail monoclonal antibodies. Breast tumor cells from luminal B and HER2 subtypes showed the most malignant profiles and the expression of thrombin and other classes of proteases at levels that were detectable through FRET peptide libraries. The angiogenesis process was investigated in the interface obtained between platelet-fibrin-breast tumor cells co-cultured with HUVEC cells. Luminal B and HER2 cells showed robust endothelial cell capillary-like tubes ex vivo. The studied interface contributes to the attachment of endothelial cells, provides a source of growth factors, and is a solid substrate. Thus, replacement of FBS supplementation with PRP supplementation represents an efficient and simple approach for mimicking the real multifactorial tumor microenvironment.en
dc.description.affiliationUniv Fed Sao Paulo, Dept Gynecol, Sao Paulo, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Biochem, Sao Paulo, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Biophys, Sao Paulo, Brazil
dc.description.affiliationCharitable Assoc Blood Collect COLSAN, Sao Paulo, SP, Brazil|Univ Sao Paulo, Ctr Nucl Energy Agr, Cell & Mol Biol Lab, Piracicaba, SP, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Gynecol, Sao Paulo, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Biochem, Sao Paulo, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Biophys, Sao Paulo, Braz
dc.description.sourceWeb of Science
dc.description.sponsorshipFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
dc.description.sponsorshipCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
dc.description.sponsorshipIDFAPESP: 2012/19780-3
dc.description.sponsorshipIDFAPESP: 2012/19851-8
dc.description.sponsorshipIDFAPESP: 2009/53766-5
dc.description.sponsorshipIDCNPq: 445229/2014-4
dc.format.extent16851-16874
dc.identifierhttp://dx.doi.org/10.18632/oncotarget.15170
dc.identifier.citationOncotarget. Orchard Park, v. 8, n. 10, p. 16851-16874, 2017.
dc.identifier.doi10.18632/oncotarget.15170
dc.identifier.issn1949-2553
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/54935
dc.identifier.wosWOS:000396024600061
dc.language.isoeng
dc.publisherImpact Journals Llc
dc.relation.ispartofOncotarget
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectplateletsen
dc.subjectbreast canceren
dc.subjectplatelet-rich plasmaen
dc.subjectcanceren
dc.subjecttumor microenvironmenten
dc.titleInterface between breast cancer cells and the tumor microenvironment using platelet-rich plasma to promote tumor angiogenesis - influence of platelets and fibrin bundles on the behavior of breast tumor cellsen
dc.typeinfo:eu-repo/semantics/article
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