Mast cells mediate malignant pleural effusion formation

被引：96

作者：

Giannou, Anastasios D. ^{[1
]}

Marazioti, Antonia ^{[1
]}

Spella, Magda ^{[1
]}

Kanellakis, Nikolaos I. ^{[2
]}

Apostolopoulou, Hara ^{[1
]}

Psallidas, Loannis ^{[1
,3
]}

Prijovich, Zeljko M. ^{[1
]}

Vreka, Malamati ^{[1
]}

Zazara, Dimitra E. ^{[1
]}

Lilis, Loannis ^{[1
]}

Papaleonidopoulos, Vassilios ^{[1
]}

Kairi, Chrysoula A. ^{[1
,4
]}

Patmanidi, Alexandra L. ^{[2
]}

Giopanou, Joanna ^{[1
]}

Spiropoulou, Nikolitsa ^{[1
]}

Harokopos, Vaggelis ^{[5
]}

Aidinis, Vassilis ^{[6
]}

Spyratos, Dionisios ^{[7
]}

Teliousi, Stamatia ^{[8
]}

Papadaki, Helen ^{[9
]}

Taraviras, Stavros ^{[2
]}

Snyder, Linda A. ^{[10
]}

Eickelberg, Oliver ^{[11
,12
]}

Kardamakis, Dimitrios ^{[13
]}

Iwakura, Voichiro ^{[14
]}

Feyerabend, Thorsten B. ^{[15
]}

Rodewald, Hans-Reimer ^{[15
]}

Kalomenidis, Loannis ^{[4
]}

Blackwell, Timothy S. ^{[16
]}

Agalloti, Theodora ^{[1
]}

Stathopoulos, Georgios T. ^{[4
,11
,12
,16
]}

机构：

[1] Univ Patras, Fac Med, Dept Physiol, Lab Mol Resp Carcinogenesis, Rion, Achaia, Greece

[2] Univ Patras, Fac Med, Dept Physiol, Stem Cell Biol Lab, Rion, Achaia, Greece

[3] Churchill Hosp, Oxford Ctr Resp Med, Oxford OX3 7LJ, England

[4] Univ Athens, Gen Hosp Evangelismos, Sch Med, Dept Crit Care & Pulm Med 1, Athens, Attica, Greece

[5] Biomed Sci Res Ctr BSRC, Express Profiling Unit, Vari, Attica, Greece

[6] Biomed Sci Res Ctr BSRC, Div Immunol, Vari, Attica, Greece

[7] Aristotle Univ Thessaloniki, Hosp G Papanikolaau, Fac Med, Dept Pulm Med, GR-54006 Thessaloniki, Greece

[8] Hosp G Papanikolaou, Dept Cytol, Thessaloniki, Greece

[9] Univ Patras, Fac Med, Dept Anat, Rion, Achaia, Greece

[10] Janssen R&D LLC, Oncol Discovery Res, Spring House, PA USA

[11] Univ Munich, Univ Hosp, CPC, Munich, Germany

[12] Helmholtz Zentrum Munchen, Munich, Germany

[13] Univ Patras, Fac Med, Dept Radiat Oncol & Stereotact Radiotherapy, Rion, Achaia, Greece

[14] Tokyo Univ Sci, Res Inst Biomed Sci, Tokyo 162, Japan

[15] Deutsch Krebsforsch Zentrum DKFZ, Div Cellular Immunol, Heidelberg, Baden Wurttembe, Germany

[16] Vanderbilt Univ, Sch Med, Dept Med, Div Allergy Pulm & Crit Care Med, Nashville, TN 37212 USA

来源：

JOURNAL OF CLINICAL INVESTIGATION | 2015年 / 125卷 / 06期

基金：

欧洲研究理事会;

关键词：

FACTOR-KAPPA-B; C-KIT GENE; LUNG ADENOCARCINOMA; TUMOR PROGRESSION; MOUSE MODEL; MICE; INFLAMMATION; ACTIVATION; DEFICIENT; PROMOTES;

D O I：

10.1172/JCI79840

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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-1 beta, which in turn induced pleural vasculature leakiness and triggered NF-kappa B 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 adenbcarcinoma 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.

引用

页码：2317 / 2334

页数：18

共 59 条

[1] Cancer-related inflammation: Common themes and therapeutic opportunities [J].

Balkwill, Frances R. ;

Mantovani, Alberto .

SEMINARS IN CANCER BIOLOGY, 2012, 22 (01) :33-40

[2] Human mast cells stimulate vascular tribe formation - Tryptase is a novel, potent angiogenic factor [J].

Blair, RJ ;

Meng, H ;

Marchese, MJ ;

Ren, SL ;

Schwartz, LB ;

Tonnesen, MG ;

Gruber, BL .

JOURNAL OF CLINICAL INVESTIGATION, 1997, 99 (11) :2691-2700

[3] Lineage-Sca1+c-Kit-CD25+ Cells Are IL-33-Responsive Type 2 Innate Cells in the Mouse Bone Marrow [J].

Brickshawana, Adipong ;

Shapiro, Virginia Smith ;

Kita, Hirohito ;

Pease, Larry R. .

JOURNAL OF IMMUNOLOGY, 2011, 187 (11) :5795-5804

[4] Pleural drainage and pleurodesis: implementation of guidelines in four hospitals [J].

Burgers, J. A. ;

Kunst, P. W. A. ;

Koolen, M. G. J. ;

Willems, L. N. A. ;

Burgers, J. S. ;

van den Heuvel, M. .

EUROPEAN RESPIRATORY JOURNAL, 2008, 32 (05) :1321-1327

[5] Shifting foci of hematopoiesis during reconstitution from single stem cells [J].

Cao, YA ;

Wagers, AJ ;

Beilhack, A ;

Dusich, J ;

Bachmann, MH ;

Negrin, RS ;

Weissman, IL ;

Contag, CH .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (01) :221-226

[6] Identification of mast cell progenitors in adult mice [J].

Chen, CC ;

Grimbaldeston, MA ;

Tsai, M ;

Weissman, IL ;

Galli, SJ .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (32) :11408-11413

[7] Adoptive Transfer of Syngeneic Bone Marrow-Derived Cells in Mice with Obesity-Induced Diabetes [J].

Chen, Jun ;

Li, Houwei ;

Addabbo, Francesco ;

Zhang, Fung ;

Pelger, Edward ;

Patschan, Daniel ;

Park, Hyeong-Cheon ;

Kuo, Mei-Chuan ;

Ni, Jei ;

Gobe, Glenda ;

Chander, Praveen N. ;

Nasjletti, Alberto ;

Goligorsky, Michael S. .

AMERICAN JOURNAL OF PATHOLOGY, 2009, 174 (02) :701-711

[8] Mast cells play a key role in neutrophil recruitment in experimental bullous pemphigoid [J].

Chen, RY ;

Ning, G ;

Zhao, ML ;

Fleming, MG ;

Diaz, LA ;

Werb, Z ;

Liu, Z .

JOURNAL OF CLINICAL INVESTIGATION, 2001, 108 (08) :1151-1158

[9] Conditional gene targeting in macrophages and granulocytes using LysMcre mice [J].

Clausen, BE ;

Burkhardt, C ;

Reith, W ;

Renkawitz, R ;

Förster, I .

TRANSGENIC RESEARCH, 1999, 8 (04) :265-277

[10] Leukocytes in Mammary Development and Cancer [J].

Coussens, Lisa M. ;

Pollard, Jeffrey W. .

COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY, 2011, 3 (03) :1-22

← 1 2 3 4 5 6 →