title: 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 tumor-associated features. Indeed, the p53/p21 response pathway to gamma-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.
authors.affiliation: Department of Biological and Medical Research, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Nahed M
authors.initials: NM
authors.lastname: Hawsawi
authors.forename: Hazem
authors.initials: H
authors.lastname: Ghebeh
authors.forename: Siti-Faujiah
authors.initials: SF
authors.lastname: Hendrayani
authors.forename: Asma
authors.initials: A
authors.lastname: Tulbah
authors.forename: Maha
authors.initials: M
authors.lastname: Al-Eid
authors.forename: Taher
authors.initials: T
authors.lastname: Al-Tweigeri
authors.forename: Dahish
authors.initials: D
authors.lastname: Ajarim
authors.forename: Ayodele
authors.initials: A
authors.lastname: Alaiya
authors.forename: Said
authors.initials: S
authors.lastname: Dermime
authors.forename: Abdelilah
authors.initials: A
authors.lastname: Aboussekhra
mesh_terms: D001943:Breast Neoplasms / Q000473:pathology*; D016923:Cell Death; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D004396:Coloring Agents; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000473:pathology* / Q000528:radiation effects; D005434:Flow Cytometry; D005720:Gamma Rays; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000032:analysis; D009363:Neoplasm Proteins / Q000032:analysis / Q000378:metabolism; D012016:Reference Values; D000077022:Survivin; D014466:Ultraviolet Rays
chemical_list: C107489:BIRC5 protein, human; D004396:Coloring Agents; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin