Identification of mechanisms controlling fibroblast functions in ductal breast carcinoma in situ.
Carina Strell and colleagues in the Arne Östman research group has published an article in Journal of the National Cancer Institute investigating mechanisms controlling fibroblast functions in ductal breast carcinoma in situ (DCIS).
A better definition of biomarkers and biological processes related to a high risk for local recurrence and disease progression is highly warranted for DCIS.
Cross-talk between the DCIS cells and surrounding cells of the tumor microenvironment epithelial interactions are likely of major importance for the biological, clinical and pathological distinctions between high and low risk DCIS cases.
This work shows that a special fibroblast profile, defined by low expression of PDGFRalpha and high expression of PDGFRbeta is a marker for high risk DCIS in two independent patient cohorts. The fibroblast phenotype was further found to be associated with beginning degradation of the basement membrane.
Detailed analyses in cell culture and mouse DCIS models could identify a molecular pathway, involving DCIS-expressed Jagged1 and Notch2 on fibroblasts as key signaling pathway for formation of the poor prognosis associated fibroblasts.
In general terms the study highlights the importance of fibroblast/DCIS crosstalk and help identify mechanisms controlling fibroblast functions.
Publication
Impact of Epithelial-Stromal Interactions on Peritumoral Fibroblasts in Ductal Carcinoma in Situ.
Strell C, Paulsson J, Jin S, Tobin N, Mezheyeuski A, Roswall P, et al
J. Natl. Cancer Inst. 2019 Feb;():