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

• Main Authors: Paulo Roberto Del Valle, Cintia Milani, Maria Mitzi Brentani, Maria Lucia Hirata Katayama, Eduardo Carneiro de Lyra, Dirce Maria Carraro, Helena Brentani, Renato Puga, Leandro A. Lima, Patricia Bortman Rozenchan, Bárbara dos Santos Nunes, João Carlos Guedes Sampaio Góes, Maria Aparecida Azevedo Koike Folgueira
• Format: Article
• Language: English
• Published: Sociedade Brasileira de Genética 2014-09-01
• Series: Genetics and Molecular Biology
• Subjects: bone marrow; breast neoplasm; fibroblast; gene expression profiling; lymph node; mesenchymal stromal cells; tumor microenvironment
• Online Access: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572014000400002&lng=en&tlng=en

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.