Upregulation of bronchioloalveolar carcinoma-derived C-X-C chemokines by tumor infiltrating inflammatory cells.
OBJECTIVE
The presence of increased numbers of tumor-infiltrating neutrophils is associated with poorer outcome in patients with adenocarcinoma of the bronchioloalveolar (BAC) subtype. We evaluated the role of inflammatory environment on C-X-C chemokine tumor production.


METHODS
Bronchoalveolar lavage from 31 consecutive patients with adenocarcinoma of the BAC subtype as well as tumor and normal pulmonary tissue samples. A549 BAC cell line. Peripheral blood mononuclear cells (PBMC), polymorphonuclear neutrophils (PMN) and alveolar macrophages (AM).


METHODS
Elisa measurements and immunohistochemical studies of ENA-78, IL-8, IL-1beta and TNF-alpha. RNA isolation, reverse transcription, and PCR amplification of ENA-78 and IL-8.


RESULTS
C-X-C peptides were expressed by tumor cells of all the tumor specimens tested. ENA-78 and IL-8 were also expressed by AM. To better understand the regulation of the C-X-C production, BAC cell line was cultured alone or with inflammatory cells. PBMC upregulated both tumor ENA-78 and IL-8 mRNA expression and protein release whereas AM only upregulated ENA-78 mRNA expression and protein release; PMN had no effect. Anti-human IL-1beta antibodies (ab) inhibited the A549 ENA-78 and IL-8 production stimulated by PBMC-CM. Anti-human TNF-alpha ab inhibited A549 ENA-78 production stimulated by AM-CM. IL-1beta and TNF-alpha were expressed in vivo by inflammatory cells, although TNF-alpha was also expressed by tumor cells.


CONCLUSIONS
This work emphasizes the role of the host inflammatory response in promoting tumor growth in vivo.
Wislez
M
M
Service de Pneumologie et de Réanimation Respiratoire, AP-HP, Hôpital Tenon, 4 rue de la chine, 75020 Paris, France.
Philippe
C
C
Antoine
M
M
Rabbe
N
N
Moreau
J
J
Bellocq
A
A
Mayaud
C
C
Milleron
B
B
Soler
P
P
Cadranel
J
J
D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D054365:Chemokine CXCL5; D019743:Chemokines, CXC / Q000378:metabolism*; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D016209:Interleukin-8 / Q000031:analogs & derivatives / Q000096:biosynthesis; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D016676:Macrophages, Alveolar; D008297:Male; D008875:Middle Aged; D009000:Monocytes; D009504:Neutrophils; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C486263:CXCL5 protein, human; D054365:Chemokine CXCL5; D019743:Chemokines, CXC; D007375:Interleukin-1; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha