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(s):Show less -

Andrade, Sheila Siqueira ; Sumikawa, Joana Tomomi ; Castro, Eloisa Dognani ; Batista, Fabricio Pereira ; Paredes-Gamero, Edgar ; Oliveira, Lilian Carolina ; Guerra, Izabel Monasterio ; Peres, Giovani Bravin ; Cavalheiro, Renan Pelluzzi ; Juliano, Luiz ; Nazario, Afonso Pinto ; Facina, Gil ; Tsai, Siu Mui ; Vilela Oliva, Maria Luiza ; Batista Castello Girao, Manoel Joao

• Document type: Journal article
• Source: ONCOTARGET; v. 8, n. 10, p. 16851-16874, 2017.
• Web of Science Citations: 12

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. (AU)

• FAPESP's process: 12/19851-8 - Heterotypic culture: The Cross-Talking between epithelial tumor cells, mammary stroma, macrophages and platelets in breast cancer: the release of proteolytic enzymes and signaling of Toll-like receptors
• Grantee: Sheila Siqueira Andrade
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 09/53766-5 - Proteins from plant source with selectivity for inhibition of mammalian enzymes and their role as an anti-inflammatory, antithrombotic, anti-diabetic and anti-tumor agent
• Grantee: Maria Luiza Vilela Oliva
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 12/19780-3 - Heterotypic culture: the cross-talking between epithelial tumor cells, mammary stroma, macrophages and platelets in breast cancer: the release of proteolytic enzymes and signaling of toll-like receptors
• Grantee: Manoel João Batista Castello Girão
• Support Opportunities: Regular Research Grants