Neutrophils promote aerogenous spread of lung adenocarcinoma with bronchioloalveolar carcinoma features. 2007

Marie Wislez, and Martine Antoine, and Nathalie Rabbe, and Valérie Gounant, and Virginie Poulot, and Armelle Lavolé, and Jocelyne Fleury-Feith, and Jacques Cadranel
Services de Pneumologie, AP-HP, Hôpital Tenon, Paris, France.

OBJECTIVE Adenocarcinoma with bronchioloalveolar carcinoma (BAC) features is a subtype of non-small cell lung cancers characterized by an intense inflammatory reaction composed of macrophages and neutrophils and by a distinct natural history with intrapulmonary spread leading to death due to respiratory failure. We hypothesized that neutrophils could promote aerogenous spread of lung adenocarcinoma with BAC features. METHODS We examined the effect of neutrophils on A549 cell line detachment in vitro and we quantified desquamation of tumor cells on tumor tissue (n = 25) and on matched bronchioloalveolar lavage (n = 17) in vivo in a series of patients with adenocarcinoma with BAC features. RESULTS Neutrophils induced A549 detachment mediated by signals through cell-to-cell contact. Detached A549 cells were still viable and able to proliferate in vitro. Neutralization studies identified several membrane-bound molecules involved in detachment (i.e., intercellular adhesion molecule-1/lymphocyte function-associated antigen-1, tumor necrosis factor alpha/tumor necrosis factor alpha receptor inhibitor, interleukin-1alpha /interleukin-1alpha receptor, and neutrophil elastase). In tumor tissue, shedding was detected in all samples, with a median shedding score of 42% (range, 4-95%). Micropapillary clusters were detected in 23 of the 25 tumor tissue samples, with a median micropapillary score of 1.40 (range, 0-2.1), and tumor cells were detected in 7 of 17 lavages. The micropapillary score was associated with a high neutrophil count in bronchioloalveolar lavage (P = 0.051). The shedding cell percentage was a significant factor in shorter survival (P = 0.034, univariate Cox analysis). CONCLUSIONS Tumor shedding is induced by neutrophils. It is a significant factor of shorter survival and may be an important event in adenocarcinoma progression.

UI MeSH Term Description Entries
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D008175 Lung Neoplasms Tumors or cancer of the LUNG. Cancer of Lung,Lung Cancer,Pulmonary Cancer,Pulmonary Neoplasms,Cancer of the Lung,Neoplasms, Lung,Neoplasms, Pulmonary,Cancer, Lung,Cancer, Pulmonary,Cancers, Lung,Cancers, Pulmonary,Lung Cancers,Lung Neoplasm,Neoplasm, Lung,Neoplasm, Pulmonary,Pulmonary Cancers,Pulmonary Neoplasm
D008297 Male Males
D009361 Neoplasm Invasiveness Ability of neoplasms to infiltrate and actively destroy surrounding tissue. Invasiveness, Neoplasm,Neoplasm Invasion,Invasion, Neoplasm
D009504 Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. LE Cells,Leukocytes, Polymorphonuclear,Polymorphonuclear Leukocytes,Polymorphonuclear Neutrophils,Neutrophil Band Cells,Band Cell, Neutrophil,Cell, LE,LE Cell,Leukocyte, Polymorphonuclear,Neutrophil,Neutrophil Band Cell,Neutrophil, Polymorphonuclear,Polymorphonuclear Leukocyte,Polymorphonuclear Neutrophil
D002282 Adenocarcinoma, Bronchiolo-Alveolar A carcinoma derived from epithelium of terminal bronchioles, in which the neoplastic tissue extends along the alveolar walls and grows in small masses within the alveoli. Involvement may be uniformly diffuse and massive, or nodular, or lobular. The neoplastic cells are cuboidal or columnar and form papillary structures. Mucin may be demonstrated in some of the cells and in the material in the alveoli, which also includes denuded cells. Metastases in regional lymph nodes, and in even more distant sites, are known to occur, but are infrequent. (From Stedman, 25th ed) Carcinoma, Alveolar,Carcinoma, Bronchiolar,Carcinoma, Bronchiolo-Alveolar,Adenocarcinoma, Alveolar,Alveolar Cell Carcinoma,Carcinoma, Bronchioloalveolar,Adenocarcinoma, Bronchiolo Alveolar,Adenocarcinomas, Alveolar,Adenocarcinomas, Bronchiolo-Alveolar,Alveolar Adenocarcinoma,Alveolar Adenocarcinomas,Alveolar Carcinoma,Alveolar Carcinomas,Alveolar Cell Carcinomas,Bronchiolar Carcinoma,Bronchiolar Carcinomas,Bronchiolo-Alveolar Adenocarcinoma,Bronchiolo-Alveolar Adenocarcinomas,Bronchiolo-Alveolar Carcinoma,Bronchiolo-Alveolar Carcinomas,Bronchioloalveolar Carcinoma,Bronchioloalveolar Carcinomas,Carcinoma, Alveolar Cell,Carcinoma, Bronchiolo Alveolar,Carcinomas, Alveolar,Carcinomas, Alveolar Cell,Carcinomas, Bronchiolar,Carcinomas, Bronchiolo-Alveolar,Carcinomas, Bronchioloalveolar
D002448 Cell Adhesion Adherence of cells to surfaces or to other cells. Adhesion, Cell,Adhesions, Cell,Cell Adhesions
D002450 Cell Communication Any of several ways in which living cells of an organism communicate with one another, whether by direct contact between cells or by means of chemical signals carried by neurotransmitter substances, hormones, and cyclic AMP. Cell Interaction,Cell-to-Cell Interaction,Cell Communications,Cell Interactions,Cell to Cell Interaction,Cell-to-Cell Interactions,Communication, Cell,Communications, Cell,Interaction, Cell,Interaction, Cell-to-Cell,Interactions, Cell,Interactions, Cell-to-Cell
D005260 Female Females
D005434 Flow Cytometry Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. Cytofluorometry, Flow,Cytometry, Flow,Flow Microfluorimetry,Fluorescence-Activated Cell Sorting,Microfluorometry, Flow,Cell Sorting, Fluorescence-Activated,Cell Sortings, Fluorescence-Activated,Cytofluorometries, Flow,Cytometries, Flow,Flow Cytofluorometries,Flow Cytofluorometry,Flow Cytometries,Flow Microfluorometries,Flow Microfluorometry,Fluorescence Activated Cell Sorting,Fluorescence-Activated Cell Sortings,Microfluorimetry, Flow,Microfluorometries, Flow,Sorting, Fluorescence-Activated Cell,Sortings, Fluorescence-Activated Cell

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