title: Nipple aspirate fluids from women with breast cancer contain increased levels of group IIa secretory phospholipase A2.
abstract: Arachidonic acid, a bioactive molecule metabolized into prostaglandins and leukotrienes, contributes to cellular proliferation and tumor progression. Group IIa secretory phospholipase A2 (sPLA2-IIa) can facilitate arachidonate release from cellular phospholipids, suggesting its involvement in tumor evolution. Analysis of breast nipple aspirate fluid (NAF), a noninvasive research tool, allows the identification of biomarkers of breast cancer. We sought to determine whether sPLA2-IIa expression might be related to breast cancer development or progression. sPLA2-IIa expression was evaluated in NAF samples from 110 women (57 women with and 53 without breast cancer) using ELISA and western blotting; ultrastructural immunolocalization was performed in epithelial cells floating in NAF. Immunocytochemistry revealed that sPLA2-IIa is a constitutive intracellular protein suggesting that breast ductal cells synthesize and secrete the 14 kDa protein in NAF. Among all 110 subjects, sPLA2-IIa expression was significantly increased both in NAF and within ductal epithelial cells from cancer containing breasts. While in healthy women menopausal status did not influence sPLA2-IIa expression (P = 0.457), among patients with breast cancer there was a significant down-regulation in postmenopausal subjects (P < 0.0001). Moreover, sPLA2-IIa concentration in NAF from breast cancer patients was positively correlated with tumor stage (r (2) = 0.979, P = 0.0012), suggesting an active secretion/accumulation of the enzyme in NAF based on tumor burden. sPLA2-IIa activity may serve a dual role in breast carcinogenesis, beneficial in its release of arachidonate and detrimental in the metabolic conversion of arachadonic acid into prostaglandins and leukotrienes.
authors.affiliation: Institute of Histology and Laboratory Analysis, Faculty of Science and Technology, University of Urbino Carlo Bo, Urbino, 61029, Italy, ferdinando.mannello@uniurb.it
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Mannello
authors.forename: Wenyi
authors.initials: W
authors.lastname: Qin
authors.forename: Weizhu
authors.initials: W
authors.lastname: Zhu
authors.forename: Laura
authors.initials: L
authors.lastname: Fabbri
authors.forename: Gaetana A
authors.initials: GA
authors.lastname: Tonti
authors.forename: Edward R
authors.initials: ER
authors.lastname: Sauter
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016718:Arachidonic Acid / Q000378:metabolism; D001826:Body Fluids / Q000378:metabolism*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D009558:Nipples / Q000378:metabolism*; D054497:Phospholipases A2, Secretory / Q000032:analysis* / Q000502:physiology; D017698:Postmenopause
chemical_list: D016718:Arachidonic Acid; D054497:Phospholipases A2, Secretory