| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Tumor Biology |
Service de Pneumologie et de Réanimation Respiratoire [M. W., J. C.], and Service d’Anatomie Pathologique [M. A.], AP-HP, Hôpital Tenon, 75020 Paris; Laboratoire de Biologie Cellulaire et d’Immunopathologie Pulmonaire, Unité Propre Recherche Enseignement Supérieur Equipe Accueil 3493, Unité Formation Recherche Saint-Antoine, Université Paris VI, 75020 Paris [M. W., N. R., B. M., C. M., M. A., J. C.]; and Unité Institut National de la Santé et de la Recherche Médicale (INSERM) 408, Unité Formation Recherche Xavier, Université Paris VII, 75018 Paris [J. M., B. C., P. S.], France
Increased numbers of tumor-infiltrating neutrophils are linked to poorer outcome in patients with adenocarcinoma of the bronchioloalveolar carcinoma (BAC) subtype. Hepatocyte growth factor (HGF) is a pleiotropic cytokine operating through activation of the proto-oncogene c-met and is a factor of poor prognosis in various cancers. Reports that neutrophils produce HGF led us to investigate their participation in the aerogenous spread of tumor cells and the prognosis of BAC, through the effect of HGF on c-met-expressing tumor cells. Immunoreactive HGF was detected in bronchoalveolar lavage fluid (BALF) supernatants from 34 of 36 patients, whereas it was undetectable in BALF from healthy controls. The HGF thus detected was locally produced, because HGF mRNA was expressed by the patients’ fresh alveolar cells, and HGF protein was detected in 24-h culture supernatants. In immunocytochemical studies of BALF cytospin preparations and tumor specimens from the patients, neutrophils were always HGF-positive, whereas alveolar macrophages and tumor cells gave inconsistent results. Alveolar neutrophil-derived HGFs induced significant, concentration-dependent migration of BAC-derived tumor cells in vitro, and this effect was inhibited by anti-HGF neutralizing antibodies. Granulocyte-macrophage colony-stimulating factor and tumor necrosis factor 
(present in the lung tumor microenvironment) provoked HGF release from neutrophil intracellular stocks, and the capacity of blood neutrophils from BAC patients to produce HGF was unaltered. Immunochemical studies of c-met expression in BALF cytospin preparations and tumor sections showed that most HGF receptor-bearing cells were tumor cells. High HGF levels in BALF supernatants were significantly associated with poorer outcome in patients with BAC and were an independent predictor of clinical outcome in multivariate analysis. Altogether, our results support the notion that BAC generates a local environment that attracts functionally normal neutrophils from peripheral blood and leads to neutrophil release of biologically active HGF on contact with HGF receptor-expressing tumor cells, thereby contributing to poorer patient outcome.
This article has been cited by other articles:
|
|
 |
|
  Y. Yang, M. Wislez, N. Fujimoto, L. Prudkin, J. G. Izzo, F. Uno, L. Ji, A. E. Hanna, R. R. Langley, D. Liu, et al. A selective small molecule inhibitor of c-Met, PHA-665752, reverses lung premalignancy induced by mutant K-ras Mol. Cancer Ther., April 1, 2008; 7(4): 952 - 960. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Iwanaga, Y. Yang, M. G. Raso, L. Ma, A. E. Hanna, N. Thilaganathan, S. Moghaddam, C. M. Evans, H. Li, W.-W. Cai, et al. Pten Inactivation Accelerates Oncogenic K-ras-Initiated Tumorigenesis in a Mouse Model of Lung Cancer Cancer Res., February 15, 2008; 68(4): 1119 - 1127. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. E. Reznik, Y. Sang, Y. Ma, R. Abounader, E. M. Rosen, S. Xia, and J. Laterra Transcription-Dependent Epidermal Growth Factor Receptor Activation by Hepatocyte Growth Factor Mol. Cancer Res., January 1, 2008; 6(1): 139 - 150. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Okunishi, M. Dohi, K. Fujio, K. Nakagome, Y. Tabata, T. Okasora, M. Seki, M. Shibuya, M. Imamura, H. Harada, et al. Hepatocyte Growth Factor Significantly Suppresses Collagen-Induced Arthritis in Mice J. Immunol., October 15, 2007; 179(8): 5504 - 5513. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Shaykhiev and R. Bals Interactions between epithelial cells and leukocytes in immunity and tissue homeostasis J. Leukoc. Biol., July 1, 2007; 82(1): 1 - 15. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Wislez, M. Antoine, N. Rabbe, V. Gounant, V. Poulot, A. Lavole, J. Fleury-Feith, and J. Cadranel Neutrophils Promote Aerogenous Spread of Lung Adenocarcinoma with Bronchioloalveolar Carcinoma Features Clin. Cancer Res., June 15, 2007; 13(12): 3518 - 3527. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.-C. Chow Correspondence The Pulmonary Source of Hepatocyte Growth Factor in Non-Small Cell Lung Cancer Am. J. Respir. Cell Mol. Biol., January 1, 2007; 36(1): 131 - 132. [Full Text] [PDF]
|
|
|
|
|
|
T. Ohnishi, K. Kakimoto, K. Bandow, C. J. Lowenstein, Y. Daikuhara, and T. Matsuguchi Mature Hepatocyte Growth Factor/Scatter Factor on the Surface of Human Granulocytes Is Released by a Mechanism Involving Activated Factor Xa. J. Immunol., June 1, 2006; 176(11): 6945 - 6953. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Bonay, A. Boutten, and B. Crestani HGF and Lung Carcinoma: Don't Forget Neutrophils. Am. J. Respir. Cell Mol. Biol., May 1, 2006; 34(5): 643 - 643. [Full Text] [PDF]
|
|
|
|
|
|
M. Wislez, N. Fujimoto, J. G. Izzo, A. E. Hanna, D. D. Cody, R. R. Langley, H. Tang, M. D. Burdick, M. Sato, J. D. Minna, et al. High expression of ligands for chemokine receptor CXCR2 in alveolar epithelial neoplasia induced by oncogenic kras. Cancer Res., April 15, 2006; 66(8): 4198 - 4207. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Queen, R. E. Ryan, R. G. Holzer, C. R. Keller-Peck, and C. L. Jorcyk Breast Cancer Cells Stimulate Neutrophils to Produce Oncostatin M: Potential Implications for Tumor Progression Cancer Res., October 1, 2005; 65(19): 8896 - 8904. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Okunishi, M. Dohi, K. Nakagome, R. Tanaka, S. Mizuno, K. Matsumoto, J.-i. Miyazaki, T. Nakamura, and K. Yamamoto A Novel Role of Hepatocyte Growth Factor as an Immune Regulator through Suppressing Dendritic Cell Function J. Immunol., October 1, 2005; 175(7): 4745 - 4753. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Wislez, M. L. Spencer, J. G. Izzo, D. M. Juroske, K. Balhara, D. D. Cody, R. E. Price, W. N. Hittelman, I. I. Wistuba, and J. M. Kurie Inhibition of Mammalian Target of Rapamycin Reverses Alveolar Epithelial Neoplasia Induced by Oncogenic K-ras Cancer Res., April 15, 2005; 65(8): 3226 - 3235. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Lantuejoul, T.V. Colby, G.R. Ferretti, P.Y. Brichon, C. Brambilla, and E. Brambilla Adenocarcinoma of the lung mimicking inflammatory lung disease with honeycombing Eur. Respir. J., September 1, 2004; 24(3): 502 - 505. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
