title: 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.
authors.affiliation: Departamento de Radiologia e Oncologia , Faculdade de Medicina , Universidade de São Paulo , São Paulo, SP , Brazil .
authors.forename: Paulo Roberto
authors.initials: PR
authors.lastname: Del Valle
authors.affiliation: Departamento de Radiologia e Oncologia , Faculdade de Medicina , Universidade de São Paulo , São Paulo, SP , Brazil .
authors.forename: Cintia
authors.initials: C
authors.lastname: Milani
authors.affiliation: Departamento de Radiologia e Oncologia , Faculdade de Medicina , Universidade de São Paulo , São Paulo, SP , Brazil .
authors.forename: Maria Mitzi
authors.initials: MM
authors.lastname: Brentani
authors.affiliation: Departamento de Radiologia e Oncologia , Faculdade de Medicina , Universidade de São Paulo , São Paulo, SP , Brazil .
authors.forename: Maria Lucia Hirata
authors.initials: ML
authors.lastname: Katayama
authors.affiliation: Instituto Brasileiro do Controle do Câncer , São Paulo, SP , Brazil .
authors.forename: Eduardo Carneiro
authors.initials: EC
authors.lastname: de Lyra
authors.affiliation: Centro Internacional de Pesquisa e Ensino , Hospital A.C. Camargo , São Paulo, SP , Brazil .
authors.forename: Dirce Maria
authors.initials: DM
authors.lastname: Carraro
authors.affiliation: Departamento de Psiquiatria , Faculdade de Medicina , Universidade de São Paulo , São Paulo, SP , Brazil .
authors.forename: Helena
authors.initials: H
authors.lastname: Brentani
authors.affiliation: Centro Internacional de Pesquisa e Ensino , Hospital A.C. Camargo , São Paulo, SP , Brazil .
authors.forename: Renato
authors.initials: R
authors.lastname: Puga
authors.affiliation: Centro Internacional de Pesquisa e Ensino , Hospital A.C. Camargo , São Paulo, SP , Brazil .
authors.forename: Leandro A
authors.initials: LA
authors.lastname: Lima
authors.affiliation: Departamento de Radiologia e Oncologia , Faculdade de Medicina , Universidade de São Paulo , São Paulo, SP , Brazil .
authors.forename: Patricia Bortman
authors.initials: PB
authors.lastname: Rozenchan
authors.affiliation: Departamento de Radiologia e Oncologia , Faculdade de Medicina , Universidade de São Paulo , São Paulo, SP , Brazil .
authors.forename: Bárbara Dos Santos
authors.initials: Bdos S
authors.lastname: Nunes
authors.affiliation: Instituto Brasileiro do Controle do Câncer , São Paulo, SP , Brazil .
authors.forename: João Carlos Guedes Sampaio
authors.initials: JC
authors.lastname: Góes
authors.affiliation: Departamento de Radiologia e Oncologia , Faculdade de Medicina , Universidade de São Paulo , São Paulo, SP , Brazil .
authors.forename: Maria Aparecida
authors.initials: MA
authors.lastname: Azevedo Koike Folgueira
keywords: bone marrow; breast neoplasm; fibroblast; gene expression profiling; lymph node; mesenchymal stromal cells; tumor microenvironment