Stromal Activation by Tumor Cells: An in Vitro Study in Breast Cancer.
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.


CONCLUSIONS
Stromal TGM2 might probably be associated with precancerous evolution at earlier stages compared to DCIS.
Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Amadeo 42, 20133 Milan , Italy. peppem1985@gmail.com.
Giuseppe
G
Merlino
Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Amadeo 42, 20133 Milan , Italy. patrizia.miodini@istitutotumori.mi.it.
Patrizia
P
Miodini
Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan , Italy. biagio.paolini@istitutotumori.mi.it.
Biagio
B
Paolini
Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan , Italy. marialuisa.carcangiu@istitutotumori.mi.it.
Maria Luisa
ML
Carcangiu
Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan , Italy. massimiliano.gennaro@istitutotumori.mi.it.
Massimiliano
M
Gennaro
Functional Genomics Core Facility, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Amadeo 42, 20133Milan, Italy. matteo.dugo@istitutotumori.mi.it.
Matteo
M
Dugo
Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Amadeo 42, 20133 Milan , Italy. mariagrazia.daidone@istitutotumori.mi.it.
Maria Grazia
MG
Daidone
Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Amadeo 42, 20133 Milan , Italy. vera.cappelletti@istitutotumori.mi.it.
Vera
V
Cappelletti
biomarkers; breast cancer; ductal carcinoma in situ; fibroblasts; gene expression profiles; in-vitro models; stroma-tumor interaction; stromal activation