Abstract
BackgroundThe normal growth and function of mammary epithelial cells depend on interactions with the supportive stroma. Alterations in this communication can lead to the progression or expansion of malignant growth. The human mammary gland contains two distinctive types of fibroblasts within the stroma. The epithelial cells are surrounded by loosely connected intralobular fibroblasts, which are subsequently surrounded by the more compacted interlobular fibroblasts. The different proximity of these fibroblasts to the epithelial cells suggests distinctive functions for these two subtypes. In this report, we compared the gene expression profiles between the two stromal subtypes.MethodsFresh normal breast tissue was collected from reduction mammoplasty patients and immediately placed into embedding medium and frozen on dry ice. Tissue sections were subjected to laser capture microscopy to isolate the interlobular from the intralobular fibroblasts. RNA was prepared and subjected to microarray analysis using the Affymetrix Human Genome U133 GeneChip®. Data was analyzed using the Affy and Limma packages available from Bioconductor. Findings from the microarray analysis were validated by RT-PCR and immunohistochemistry.ResultsNo statistically significant difference was detected between the gene expression profiles of the interlobular and intralobular fibroblasts by microarray analysis and RT-PCR. However, for some of the genes tested, the protein expression patterns between the two subtypes of fibroblasts were significantly different.ConclusionThis study is the first to report the gene expression profiles of the two distinct fibroblast populations within the human mammary gland. While there was no significant difference in the gene expression profiles between the groups, there was an obvious difference in the expression pattern of several proteins tested. This report also highlights the importance of studying gene regulation at both the transcriptional and post-translational level.
Highlights
The normal growth and function of mammary epithelial cells depend on interactions with the supportive stroma
Studies targeted towards understanding the function of normal breast stroma will facilitate the development of methods for preventing breast cancer metastasis
This study provided the first data causally linking increased stromal collagen to mammary tumor formation and metastasis, and demonstrated that fundamental differences arise and persist in epithelial tumor cells that progressed within collagen-dense microenvironments
Summary
The normal growth and function of mammary epithelial cells depend on interactions with the supportive stroma. Alterations in this communication can lead to the progression or expansion of malignant growth. The different proximity of these fibroblasts to the epithelial cells suggests distinctive functions for these two subtypes. Metastasis of the tumor is the primary cause of morbidity and mortality. In late-stage breast cancer, tumor metastasis can be found in several tissues, including bone, lung, lymph node, and liver [2]. Tumor progression and metastasis are both regulated by the surrounding microenvironment, i.e. the local stroma. Studies targeted towards understanding the function of normal breast stroma will facilitate the development of methods for preventing breast cancer metastasis
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