Molecular profiling of microinvasive breast cancer microenvironment progression

Autor: Paolo Aretini, C.M. Mazzanti, Cristian Scatena, Francesca Lessi, Michele Menicagli, Antonio Giuseppe Naccarato, Sara Franceschi
Rok vydání: 2018
Předmět:
0301 basic medicine
Cancer microenvironment
Stromal cell
Breast cancer
Cancer progression
Laser capture microdissection
RNA-seq
Cell
lcsh:Medicine
Breast Neoplasms
Biology
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
0302 clinical medicine
Stroma
medicine
Tumor Microenvironment
Humans
Neoplasm Invasiveness
Breast
skin and connective tissue diseases
Neoplasm Staging
Tumor microenvironment
Sequence Analysis
RNA
Carcinoma in situ
Gene Expression Profiling
Research
lcsh:R
High-Throughput Nucleotide Sequencing
General Medicine
medicine.disease
Epithelium
Gene Expression Regulation
Neoplastic
030104 developmental biology
medicine.anatomical_structure
Carcinoma
Intraductal
Noninfiltrating
Tumor progression
030220 oncology & carcinogenesis
Cancer research
Disease Progression
Female
Stromal Cells
Metabolic Networks and Pathways
Zdroj: Journal of Translational Medicine
Journal of Translational Medicine, Vol 17, Iss 1, Pp 1-13 (2019)
ISSN: 1479-5876
Popis: Background Tumors develop by progression through a series of stages. Every cell of the tumor microenvironment is constantly changing in the flow of the cancer progression. It has become clear in recent years that stroma is essential for tumor maintenance and growth. Here, we aimed to give a chronological order of gene expression changes given in the dynamical framework of microinvasive breast cancer microenvironment. Methods RNA-seq was performed on seven microinvasive breast cancers. For each of them we microdissected seven different portions of the tumor, four related to the breast epithelium and three to the stroma. Breast epithelium was chronologically subdivided in normal breast epithelium (NBE), carcinoma in situ (CIS), emerging invasive fingers (EIF) and invasive breast cancer (IBC). For each of the breast epithelium subdivisions we collected the adjacent stroma (S): S-NBE, S-EIF and S-IBC. Results The overall differentially expressed genes (DEGs) in all the compartments were analysed and evaluated to understand the pathways involved in tumor progression. Then we analysed the DEGs of the epithelial and stromal portions in comparison with the normal portions. We observed that the stromal cells are necessary for the development and the maintenance of the tumor, especially in tumor progression. Moreover the most important genes involved in the main metabolic pathways were analysed and the communications within the different cell compartments were highlighted. Conclusions As a future perspective, a deeply study of the identified key genes, particularly in the stromal cells, will be crucial to develop an anticancer therapy that is undergoing a conversion from a cancer cell-centric strategy to a stroma-centric strategy, more genomically stable. Electronic supplementary material The online version of this article (10.1186/s12967-019-1936-x) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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