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Microarrays 2016, 5(2), 10; doi:10.3390/microarrays5020010
Stromal Activation by Tumor Cells: An in Vitro Study in Breast Cancer
Giuseppe Merlino 1, Patrizia Miodini 1, Biagio Paolini 2, Maria Luisa Carcangiu 2, Massimiliano Gennaro 3, Matteo Dugo 4, Maria Grazia Daidone 1
and Vera Cappelletti 1,*
and Vera Cappelletti 1,*
1
Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Amadeo 42, 20133 Milan , Italy
2
Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan , Italy
3
Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan , Italy
4
Functional Genomics Core Facility, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Amadeo 42, 20133Milan, Italy
*
Author to whom correspondence should be addressed.
Academic Editor: Massimo Negrini
Received: 31 March 2016 / Revised: 6 May 2016 / Accepted: 10 May 2016 / Published: 18 May 2016
(This article belongs to the Special Issue Diagnostic, Prognostic and Predictive Cancer Biomarkers)
Abstract
Background: The tumor microenvironment participates in the regulation of tumor progression and influences treatment sensitivity. In breast cancer, it also may play a role in determining the fate of non-invasive lesions such as ductal carcinoma in situ (DCIS), a non-obligate precursor of invasive diseases, which is aggressively treated despite its indolent nature in many patients since no biomarkers are available to predict the progression of DCIS to invasive disease. In vitro models of stromal activation by breast tumor cells might provide clues as to specific stromal genes crucial for the transition from DCIS to invasive disease. Methods: normal human dermal fibroblasts (NHDF) were treated under serum-free conditions with cell culture media conditioned by breast cancer cell lines (SkBr3, MDA-MB-468, T47D) for 72 h and subjected to gene expression profiling with Illumina platform. Results: TGM2, coding for a tissue transglutaminase, was identified as candidate gene for stromal activation. In public transcriptomic datasets of invasive breast tumors TGM2 expression proved to provide prognostic information. Conversely, its role as an early biosensor of tumor invasiveness needs to be further investigated by in situ analyses. Conclusion: Stromal TGM2 might probably be associated with precancerous evolution at earlier stages compared to DCIS. View Full-TextKeywords:
breast cancer; stroma-tumor interaction; stromal activation; fibroblasts; biomarkers; ductal carcinoma in situ; in-vitro models; gene expression profiles
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Merlino, G.; Miodini, P.; Paolini, B.; Carcangiu, M.L.; Gennaro, M.; Dugo, M.; Daidone, M.G.; Cappelletti, V. Stromal Activation by Tumor Cells: An in Vitro Study in Breast Cancer. Microarrays 2016, 5, 10.
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