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Mast cells mediate malignant pleural effusion formation.
- Source :
-
The Journal of clinical investigation [J Clin Invest] 2015 Jun; Vol. 125 (6), pp. 2317-34. Date of Electronic Publication: 2015 Apr 27. - Publication Year :
- 2015
-
Abstract
- Mast cells (MCs) have been identified in various tumors; however, the role of these cells in tumorigenesis remains controversial. Here, we quantified MCs in human and murine malignant pleural effusions (MPEs) and evaluated the fate and function of these cells in MPE development. Evaluation of murine MPE-competent lung and colon adenocarcinomas revealed that these tumors actively attract and subsequently degranulate MCs in the pleural space by elaborating CCL2 and osteopontin. MCs were required for effusion development, as MPEs did not form in mice lacking MCs, and pleural infusion of MCs with MPE-incompetent cells promoted MPE formation. Once homed to the pleural space, MCs released tryptase AB1 and IL-1β, which in turn induced pleural vasculature leakiness and triggered NF-κB activation in pleural tumor cells, thereby fostering pleural fluid accumulation and tumor growth. Evaluation of human effusions revealed that MCs are elevated in MPEs compared with benign effusions. Moreover, MC abundance correlated with MPE formation in a human cancer cell-induced effusion model. Treatment of mice with the c-KIT inhibitor imatinib mesylate limited effusion precipitation by mouse and human adenocarcinoma cells. Together, the results of this study indicate that MCs are required for MPE formation and suggest that MC-dependent effusion formation is therapeutically addressable.
- Subjects :
- Adenocarcinoma drug therapy
Adenocarcinoma genetics
Adenocarcinoma metabolism
Adenocarcinoma pathology
Animals
Benzamides pharmacology
Cell Line, Tumor
Colonic Neoplasms drug therapy
Colonic Neoplasms genetics
Colonic Neoplasms metabolism
Colonic Neoplasms pathology
Humans
Imatinib Mesylate
Interleukin-1beta genetics
Interleukin-1beta metabolism
Lung Neoplasms diet therapy
Lung Neoplasms genetics
Lung Neoplasms metabolism
Lung Neoplasms pathology
Male
Mast Cells pathology
Mice
Mice, Inbred NOD
Mice, SCID
Mice, Transgenic
Piperazines pharmacology
Pleural Cavity metabolism
Pleural Cavity pathology
Pleural Effusion, Malignant drug therapy
Pleural Effusion, Malignant genetics
Pleural Effusion, Malignant pathology
Protein Kinase Inhibitors pharmacology
Proto-Oncogene Proteins c-kit antagonists & inhibitors
Proto-Oncogene Proteins c-kit genetics
Proto-Oncogene Proteins c-kit metabolism
Pyrimidines pharmacology
Tryptases genetics
Tryptases metabolism
Mast Cells metabolism
Pleural Effusion, Malignant metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1558-8238
- Volume :
- 125
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- The Journal of clinical investigation
- Publication Type :
- Academic Journal
- Accession number :
- 25915587
- Full Text :
- https://doi.org/10.1172/JCI79840