Interactions with fibroblasts are distinct in Basal-like and luminal breast cancers.
Basal-like breast cancers have several well-characterized distinguishing molecular features, but most of these are features of the cancer cells themselves. The unique stromal-epithelial interactions, and more generally, microenvironmental features of basal-like breast cancers have not been well characterized. To identify characteristic microenvironment features of basal-like breast cancer, we performed cocultures of several basal-like breast cancer cell lines with fibroblasts and compared these with cocultures of luminal breast cancer cell lines with fibroblasts. Interactions between basal-like cancer cells and fibroblasts induced expression of numerous interleukins and chemokines, including IL-6, IL-8, CXCL1, CXCL3, and TGFβ. Under the influence of fibroblasts, basal-like breast cancer cell lines also showed increased migration in vitro. Migration was less pronounced for luminal lines; but, these lines were more likely to have altered proliferation. These differences were relevant to tumor biology in vivo, as the gene set that distinguished luminal and basal-like stromal interactions in coculture also distinguishes basal-like from luminal tumors with 98% accuracy in 10-fold cross-validation and 100% accuracy in an independent test set. However, comparisons between cocultures where cells were in direct contact and cocultures where interaction was solely through soluble factors suggest that there is an important impact of direct cell-to-cell contact. The phenotypes and gene expression changes invoked by cancer cell interactions with fibroblasts support the microenvironment and cell-cell interactions as intrinsic features of breast cancer subtypes.
Department of Epidemiology, University of North Carolina at Chapel Hill, Campus Box 7435, 135 Dauer Ln, Chapel Hill, NC 27599, USA.
J Terese
JT
Camp
Fathi
F
Elloumi
Erick
E
Roman-Perez
Jessica
J
Rein
Delisha A
DA
Stewart
J Chuck
JC
Harrell
Charles M
CM
Perou
Melissa A
MA
Troester
D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D002450:Cell Communication; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018925:Chemokines / Q000235:genetics; D016000:Cluster Analysis; D018920:Coculture Techniques; D005260:Female; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D007378:Interleukins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D059016:Tumor Microenvironment / Q000235:genetics
D018925:Chemokines; D007378:Interleukins