Influence of the interaction between nodal fibroblast and breast cancer cells on gene expression.
Our aim was to evaluate the interaction between breast cancer cells and nodal fibroblasts, by means of their gene expression profile. Fibroblast primary cultures were established from negative and positive lymph nodes from breast cancer patients and a similar gene expression pattern was identified, following cell culture. Fibroblasts and breast cancer cells (MDA-MB231, MDA-MB435, and MCF7) were cultured alone or co-cultured separated by a porous membrane (which allows passage of soluble factors) for comparison. Each breast cancer lineage exerted a particular effect on fibroblasts viability and transcriptional profile. However, fibroblasts from positive and negative nodes had a parallel transcriptional behavior when co-cultured with a specific breast cancer cell line. The effects of nodal fibroblasts on breast cancer cells were also investigated. MDA MB-231 cells viability and migration were enhanced by the presence of fibroblasts and accordingly, MDA-MB435 and MCF7 cells viability followed a similar pattern. MDA-MB231 gene expression profile, as evaluated by cDNA microarray, was influenced by the fibroblasts presence, and HNMT, COMT, FN3K, and SOD2 were confirmed downregulated in MDA-MB231 co-cultured cells with fibroblasts from both negative and positive nodes, in a new series of RT-PCR assays. In summary, transcriptional changes induced in breast cancer cells by fibroblasts from positive as well as negative nodes are very much alike in a specific lineage. However, fibroblasts effects are distinct in each one of the breast cancer lineages, suggesting that the inter-relationships between stromal and malignant cells are dependent on the intrinsic subtype of the tumor.
Santos
Rosângela Portilho Costa
RP
Departamento de Radiologia e Oncologia, LIM24, Faculdade de Medicina, Universidade de São Paulo, Avenida Dr. Arnaldo, 455, 4º andar, sala 4124, CEP: 01246-903 São Paulo, SP, Brazil.
Benvenuti
Ticiana Thomazine
TT
Honda
Suzana Terumi
ST
Del Valle
Paulo Roberto
PR
Katayama
Maria Lucia Hirata
ML
Brentani
Helena Paula
HP
Carraro
Dirce Maria
DM
Rozenchan
Patrícia Bortman
PB
Brentani
Maria Mitzi
MM
de Lyra
Eduardo Carneiro
EC
Torres
César Henrique
CH
Salzgeber
Marcia Batista
MB
Kaiano
Jane Haruko Lima
JH
Góes
João Carlos Sampaio
JC
Folgueira
Maria Aparecida Azevedo Koike
MA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D002465:Cell Movement; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D005347:Fibroblasts / Q000473:pathology*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D009363:Neoplasm Proteins; D012333:RNA, Messenger
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