Fimbrial cells exposure to catalytic iron mimics carcinogenic changes

• Published in: International journal of gynecological cancer Vol. 25; no. 3; pp. 389 - 398
• Main Authors: Lattuada, Debora, Uberti, Francesca, Colciaghi, Barbara, Morsanuto, Vera, Maldi, Elena, Squarzanti, Diletta Francesca, Molinari, Claudio, Boldorini, Renzo, Bulfoni, Alessandro, Colombo, Paola, Bolis, Giorgio
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group LTD 01.03.2015
• Subjects: Cell Survival - drug effects; Cell Transformation, Neoplastic - chemically induced; Cells, Cultured; Dose-Response Relationship, Drug; Epithelial Cells - chemistry; Epithelial Cells - drug effects; Epithelial Cells - pathology; Extracellular Signal-Regulated MAP Kinases - analysis; Fallopian Tubes - cytology; Female; Humans; Iron - administration & dosage; Iron - adverse effects; Ki-67 Antigen - analysis; Menstruation; Models, Biological; Nitric Oxide - biosynthesis; Ovarian cancer; Oxidative Stress - drug effects; Phosphatidylinositol 3-Kinases - analysis; Proto-Oncogene Proteins c-akt - analysis; Proto-Oncogene Proteins c-myc - analysis; ras Proteins - analysis; Tumor Suppressor Protein p53 - analysis
• ISSN: 1048-891X; 1525-1438
• DOI: 10.1097/IGC.0000000000000379

Recent evidence strongly suggests that the fallopian tube is a site of origin of ovarian cancer. Although histological data show iron deposition in the fallopian tubes, its role remains unclear. To establish whether catalytic iron has a possible role in ovarian carcinogenesis, we isolated human fimbrial secretory epithelial cells (FSECs). Fimbrial secretory epithelial cells, isolated from women undergoing isteroannessiectomy, were treated with different doses of catalytic iron (0.05-100 mM) to study cell viability; NO production; p53, Ras, ERK/MAPK, PI3K/Akt, Ki67, and c-Myc protein expressions through Western blot analysis; and immunocytochemistry or immunofluorescence. In FSECs treated with catalytic iron for up to 6 days, we observed an increase in cell viability, NO production, and p53, pan-Ras, ERK/MAPK, PI3K/Akt, Ki67, and c-Myc activations (P < 0.05) in a dose-dependent and time-dependent manner. These same results were also observed in FSECs maintained for respectively 2 and 4 weeks in the absence of catalytic iron after 6 days of stimulation. Our model aimed at studying the main nongenetic risk factor for ovarian cancer, providing an alternative interpretation for the role of menstruation in increasing risk of this pathology. This in vitro model mimics several features of the precursor lesions and opens new scenarios for further investigations regarding the correlation between damages produced by repeated retrograde menstruation carcinogenic stimuli.