title: Role of prostaglandin E2 in the invasiveness, growth and protection of cancer cells in malignant pleuritis.
abstract: The recurrence of pleural effusions is a common event in a variety of neoplastic diseases. The objective of this study was to identify the mechanisms promoting the homing and growth of cancer cells within the pleural space. A cancer cell line recovered from malignant pleural fluids (lung adenocarcinoma cell line) that constitutively expresses cyclooxygenase 2 (COX-2) and all types of prostaglandin receptors was studied. It was first demonstrated using a matrigel system, that malignant pleural fluids increase the invasiveness of adenocarcinoma cells more than congestive heart failure (CHF) pleural fluids. Moreover, exposure to exudative malignant, but not to CHF pleural fluids, increased the mRNA (measured by real-time polymerase chain reaction (PCR)) and protein expression of COX-2 (measured by Western blot), as well as the activation and nuclear translocation of nuclear factor kappaB (NFkappaB) in cancer cells. These events are all actively regulated by prostaglandin E2 (PGE2), since the addition of synthetic PGE2 to cancer cells and the depletion of PGE2 from malignant pleural fluids or the inhibition of COX-2 activity significantly increased and reduced these phenomena, respectively. Moreover, malignant pleural effusions and synthetic PGE2 increased the long-term proliferation of cancer cells and reverted the impairment in long-term proliferation due to talc exposure. This study demonstrates that PGE2 present in malignant effusions contributes to cancer expansion and may protect cancer cells by anti-proliferative effects induced by talc.
authors.affiliation: Istituto di Biomedicina e Immunologia Molecolare, Consiglio Nazionale delle Ricerche, Via Ugo La Malfa, 153, 90146 Palermo, Italy. pace@ibim.cnr.it
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Pace
authors.forename: Liboria
authors.initials: L
authors.lastname: Siena
authors.forename: Maria
authors.initials: M
authors.lastname: Ferraro
authors.forename: Mirella
authors.initials: M
authors.lastname: Profita
authors.forename: Patrizia
authors.initials: P
authors.lastname: Mondello
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Chiappara
authors.forename: Angela Marina
authors.initials: AM
authors.lastname: Montalbano
authors.forename: Antonino
authors.initials: A
authors.lastname: Giarratano
authors.forename: Giovanni
authors.initials: G
authors.lastname: Bonsignore
authors.forename: Mark
authors.initials: M
authors.lastname: Gjomarkaj
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000502:physiology*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism*; D016066:Pleural Effusion, Malignant / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D010998:Pleurisy / Q000378:metabolism / Q000473:pathology*; D018078:Receptors, Prostaglandin E / Q000378:metabolism; D013627:Talc / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016328:NF-kappa B; D009363:Neoplasm Proteins; D018078:Receptors, Prostaglandin E; D013627:Talc; D051546:Cyclooxygenase 2; D015232:Dinoprostone