Transcriptional profile of fibroblasts obtained from the primary site, lymph node and bone marrow of breast cancer patients

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.

Cancer-associated fibroblast heterogeneity in axillary lymph nodes drives metastases in breast cancer through complementary mechanisms

“…The transcriptomic signatures of CAF subsets from LN validated molecular similarities between CAF-S1 (or CAF-S4) from PT and LN. If few studies addressed CAF transcriptomic profiles in both PTs and LNs from BC patients 37,69 , a short gene list identified in ref. 37 allows to discriminate LN from PT bulk samples.…”

Cancer-associated fibroblasts modulate growth factor signaling and extracellular matrix remodeling to regulate tumor metastasis

“…Moreover, recent reports indicate that CAFs are present at secondary tumor sites [46,47]. However, more studies are needed to better understand the roles of CAFs in metastatic tumors.…”

Role of the Tumor Microenvironment in Breast Cancer

“…Despite their regular morphology, several studies have revealed that CAF have distinct mRNA and protein expression profiles that distinguish them from fibroblasts in adjacent normal breast tissue [4]. For example, they show increased expression of genes related to development and morphogenesis, such as NOTCH2 [4,26]. Additionally, a bidirectional signaling pathway between CAF and cancer cells suggests that CAF might influence the transcriptional profile of breast cancer cells [4].…”