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

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

Author Andrade, Sheila Siqueira Autor UNIFESP Google Scholar
Sumikawa, Joana Tomomi Autor UNIFESP Google Scholar
Castro, Eloisa Dognani Autor UNIFESP Google Scholar
Batista, Fabricio Pereira Autor UNIFESP Google Scholar
Paredes-Gamero, Edgar Autor UNIFESP Google Scholar
Oliveira, Lilian Carolina Google Scholar
Guerra, Izabel Monasterio Autor UNIFESP Google Scholar
Peres, Giovani Bravin Autor UNIFESP Google Scholar
Cavalheiro, Renan Pelluzzi Autor UNIFESP Google Scholar
Juliano, Luiz Google Scholar
Nazario, Afonso Pinto Autor UNIFESP Google Scholar
Facina, Gil Autor UNIFESP Google Scholar
Tsai, Siu Mui Google Scholar
Vilela Oliva, Maria Luiza Autor UNIFESP Google Scholar
Batista Castello Girao, Manoel Joao Autor UNIFESP Google Scholar
Abstract Cancer 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.
Keywords platelets
breast cancer
platelet-rich plasma
cancer
tumor microenvironment
xmlui.dri2xhtml.METS-1.0.item-coverage Orchard Park
Language English
Sponsor Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
Grant number FAPESP: 2012/19780-3
FAPESP: 2012/19851-8
FAPESP: 2009/53766-5
CNPq: 445229/2014-4
Date 2017
Published in Oncotarget. Orchard Park, v. 8, n. 10, p. 16851-16874, 2017.
ISSN 1949-2553 (Sherpa/Romeo, impact factor)
Publisher Impact Journals Llc
Extent 16851-16874
Origin http://dx.doi.org/10.18632/oncotarget.15170
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000396024600061
URI https://repositorio.unifesp.br/handle/11600/54935

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