Abstract
BackgroundTumors 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.MethodsRNA-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.ResultsThe 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.ConclusionsAs 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.
Highlights
Tumors develop by progression through a series of stages
It is important to integrate gene expression changes of both tumoral cells and cancer-associated stroma, occurring during the difference phases of tumor progression. For this reason we focused our attention on a specific kind of breast cancer such as the microinvasive breast carcinoma (MIBC), which is a rare entity in which an invasive component not exceeding 1 mm is found, mostly in a ductal carcinoma in situ (DCIS) setting [5]
Laser capture microdissection (LCM) areas Breast epithelium was chronologically divided into normal breast epithelium (NBE), carcinoma in situ (CIS), emerging invasive fingers (EIF) and invasive breast cancer (IBC) (Fig. 1A–C)
Summary
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. Tumors develop by progression through a series of stages. The possible role of the tumor microenvironment in neoplastic development has been investigated since the late nineteenth century, with studies published by Stefano Paget in 1989. Breast cancer carcinogenesis is well known, characterized by well defined stages, starting from the atypical ductal hyperplasia progressing to ductal carcinoma in situ (DCIS) and ending, not necessarily, with the invasive breast cancer (IBC). Breast cancer carcinogenesis is well known, characterized by well defined stages, starting from the atypical ductal hyperplasia progressing to ductal carcinoma in situ (DCIS) and ending, not necessarily, with the invasive breast cancer (IBC). [2]
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