Breast Carcinoma–Associated Fibroblasts and Their Counterparts Display Neoplastic-Specific Changes

Abstract

It has become clear that the initiation and progression of carcinomas depend not only on alterations in epithelial cells, but also on changes in their microenvironment. To identify these changes, we have undertaken cellular and molecular characterization of carcinoma-associated fibroblasts (CAF) and their tumor counterpart fibroblasts (TCF) isolated from 12 breast cancer patients. Normal breast fibroblasts (NBF) from plastic surgery were used as normal control. We present evidence that both CAFs and TCFs are myofibroblasts and show tumorassociated features. Indeed, the p53/p21 response pathway to ;-rays was defective in 70% CAFs, whereas it was normal in all the TCF and NBF cells. In addition, the basal levels of the p53 and p21 proteins were significantly low in 83% of CAFs and modulated in the majority of TCFs compared with NBFs. Interestingly, both TCFs and CAFs expressed high levels of the cancer marker survivin and consequently exhibited high resistance to cisplatin and UV light. Moreover, most CAFs were positive for the proliferation marker Ki-67 and exhibited high proliferation rate compared with NBFs and TCFs. However, proliferating cell nuclear antigen was highly expressed in both CAFs and TCFs. Using the two-dimensional gel electrophoresis technique, we have also shown that CAF, TCF, and NBF cells present different proteome profiles, with many proteins differentially expressed between these cells. Taken together these results indicate that different genetic alterations can occur in breast CAFs and their corresponding adjacent counterparts, showing the important role that stroma could play in breast carcinogenesis and treatment. [Cancer Res 2008;68(8):2717-25]

Breast cancer-associated fibroblasts induce epithelial-to-mesenchymal transition in breast cancer cells

“…These two groups of fibroblasts differed in terms of CXCL12 secretion and a-SMA expression. While some studies have found that a-SMA by immunohistochemistry is only observed in CAFs, not NBFs (Giannoni et al 2010, Huang et al 2010, other studies, like ours, have found that a-SMA is expressed by both CAFs and NBFs (Lebret et al 2007, Hawsawi et al 2008, Holliday et al 2009), but at higher levels in the CAFs by western blotting (Lebret et al 2007).…”

Prevalence ofPIK3CAmutations and the SNP rs17849079 in Arab breast cancer patients

“…48 Isolated CAFs were cultured in a 5% CO 2 incubator at 37 °C in Medium 199 and Ham's F12 mixed 1:1 and supplemented with 10% FCS and 1% Pen/Strep. Genomic DNA isolation.…”

Fibroblasts associated with cancer cells keep enhanced migration activity after separation from cancer cells: A novel character of tumor educated fibroblasts

“…This recruitment step is called the 'desmoplastic reaction' and is a kinetic sequence of events in the invasion process. Within the cancer tissue, the fibroblasts directly communicate with the cancer cells and other types of stromal cells and acquire a specific biological phenotype (8,9). The type of fibroblast in cancer tissue that has acquired a specific biological phenotype is called cancer-associated fibroblast (CAF), and such fibroblasts have been postulated to perform supportive roles that promote tumor progression and metastasis by secreting growth factors (10,11), chemokines (12,13), and matrix metalloproteinases (MMPs) (14,15).…”