Abstract
Cancer-associated fibroblasts (CAF) influence tumor development at primary as well as in metastatic sites, but there have been no direct comparisons of the transcriptional profiles of stromal cells from different tumor sites. In this study, we used customized cDNA microarrays to compare the gene expression profile of stromal cells from primary tumor (CAF, n = 4), lymph node metastasis (N+, n = 3) and bone marrow (BM, n = 4) obtained from breast cancer patients. Biological validation was done in another 16 samples by RT-qPCR. Differences between CAF vs N+, CAF vs BM and N+ vs BM were represented by 20, 235 and 245 genes, respectively (SAM test, FDR < 0.01). Functional analysis revealed that genes related to development and morphogenesis were overrepresented. In a biological validation set, NOTCH2 was confirmed to be more expressed in N+ (vs CAF) and ADCY2, HECTD1, HNMT, LOX, MACF1, SLC1A3 and USP16 more expressed in BM (vs CAF). Only small differences were observed in the transcriptional profiles of fibroblasts from the primary tumor and lymph node of breast cancer patients, whereas greater differences were observed between bone marrow stromal cells and the other two sites. These differences may reflect the activities of distinct differentiation programs.
Highlights
Fibroblasts are mesenchymal cells derived from the mesoderm and are involved in maintaining tissue architecture
Cancer-associated fibroblasts (CAF) are the most prominent cell type in the stroma of primary tumors. These CAFs are qualitatively different from normal fibroblasts (Orimo et al, 2005) and heterotypic interactions between cancer cells and stromal cells lead to malignant cell proliferation and metastasis
Among eight patients who had bone marrow aspirates collected during surgery, three tested positive for cytokeratin 19 expression (BMMC_3, BMMC_4, BMMC_6, Table 1)
Summary
Fibroblasts are mesenchymal cells derived from the mesoderm and are involved in maintaining tissue architecture. These cells secrete a variety of soluble factors that modulate surrounding cell functions. Cancer-associated fibroblasts (CAF) are the most prominent cell type in the stroma of primary tumors. These CAFs are qualitatively different from normal fibroblasts (Orimo et al, 2005) and heterotypic interactions between cancer cells and stromal cells lead to malignant cell proliferation and metastasis. The loss of tumor suppressor genes such as PTEN (Trimboli et al, 2009) or TP53 (Patocs et al, 2007) in stromal fibroblasts results in the activation of pathways leading to epithelial cell carcinogenesis or regional node involvement. A metabolic partnership between catabolic fibroblasts and anabolic cancer cells creates a nutrient-rich environment, even under hypoxia, that supports tumor growth (Martinez-Outschoorn et al, 2014)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
