TY - JOUR T1 - A conditional contribution of mast cells to malignant pleural effusion JF - European Respiratory Journal JO - Eur Respir J VL - 42 IS - Suppl 57 SP - 1517 AU - Anastasios D. Giannou AU - Zeljko Prijovic AU - Antonia Marazioti AU - Magda Spella AU - Chryssoula Kairi AU - Ioanna Giopanou AU - Vasilis Papaleonidopoulos AU - Dimitris Kardamakis AU - Ioannis Kalomenidis AU - Georgios T. Stathopoulos Y1 - 2013/09/01 UR - http://erj.ersjournals.com/content/42/Suppl_57/1517.abstract N2 - Although mast cells (MC) have been identified in various tumors, their role remains controversial. We accidentaly identified MC in malignant pleural effusions (MPE) and solid tumors of humans and mice, hidden in conventional stains. In C57BL/6 mice, MPE-competent LLC lung and MC38 colon adenocarcinoma cells attracted MC, whether injected intrapleurally or subcoutaneously, in contrast to MPE-incompetent B16F10 melanoma cells. To this end, CCL2 was found to be a major tumor-derived MC chemoattractant, since CCL2-silenced LLC cells lost their ability for MC recruitment, a phenotype rescued by CCL2 overexpression in B16F10 cells. Intrapleural co-transplantation of bone marrow-derived MC with B16F10 cells enhanced MPE formation by these cells. MC-deficient mice (cKitWsh) were protected from LLC-, but not from MC38-induced MPE, indicating a conditional requirement for MC in MPE development. The protection of cKitWsh mice specifically from LLC-induced MPE was ablated by adoptive bone marrow transfer (BMT) of MC-competent wt donors and was transplantable to wt mice by cKitWsh BMT. This conditional protection was associated with osteopontin (SPP1) deficiency of LLC-triggered MPEs in cKitWsh hosts, indicating that MC can serve to supplement pleural SPP1 levels during MPE formation. To this end, MC38 cells produced more SPP1 than LLC cells in vitro, and incubation of naïve MC with LLC- and MC38-, but not B16F10-conditioned media triggered de novo SPP1 elaboration. SPP1 silencing in MC38 cells rendered cKitWsh mice protected against MPE induction. Finally, imatinib mesylate treatment inhibited LLC-induced but not MC38-induced MPE, indicating a druggable and conditional requirement for MC in MPE.Supported by ERC Grant. ER -