| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
B and JNK1
* Cancer Research U.K., Translational Oncology Laboratory, Barts and The London, Queen Mary’s School of Medicine and Dentistry, London, United Kingdom; and Department of Haematology and Oncology, Georg-August-University, Göttingen, Germany
Tumor-associated macrophages may influence tumor progression, angiogenesis and invasion. To investigate mechanisms by which macrophages interact with tumor cells, we developed an in vitro coculture model. Previously we reported that coculture enhanced invasiveness of the tumor cells in a TNF-
- and matrix metalloprotease-dependent manner. In this report, we studied intracellular signaling pathways and induction of inflammatory genes in malignant cells under the influence of macrophage coculture. We report that coculture of macrophages with ovarian or breast cancer cell lines led to TNF--dependent activation of JNK and NF-
B pathways in tumor cells, but not in benign immortalized epithelial cells. Tumor cells with increased JNK and NF-B activity exhibited enhanced invasiveness. Inhibition of the NF-B pathway by TNF- neutralizing Abs, an NF-B inhibitor, RNAi to RelA, or overexpression of IB inhibited tumor cell invasiveness. Blockade of JNK also significantly reduced invasiveness, but blockade of p38 MAPK or p42 MAPK had no effect. Cocultured tumor cells were screened for the expression of 22 genes associated with inflammation and invasion that also contained an AP-1 and NF-B binding site. EMMPRIN and MIF were up-regulated in cocultured tumor cells in a JNK- and NF-B-dependent manner. Knocking down either MIF or EMMPRIN by RNAi in the tumor cells significantly reduced tumor cell invasiveness and matrix metalloprotease activity in the coculture supernatant. We conclude that TNF-, via NF-B, and JNK induces MIF and EMMPRIN in macrophage to tumor cell cocultures and this leads to increased invasive capacity of the tumor cells.
This article has been cited by other articles:
|
|
 |
|
  G. Solinas, G. Germano, A. Mantovani, and P. Allavena Tumor-associated macrophages (TAM) as major players of the cancer-related inflammation J. Leukoc. Biol., November 1, 2009; 86(5): 1065 - 1073. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Wan, J. M. C. Coppens, C. G. van Helden-Meeuwsen, P. J. M. Leenen, N. van Rooijen, N. A. Khan, R. C. M. Kiekens, R. Benner, and M. A. Versnel Chorionic gonadotropin alleviates thioglycollate-induced peritonitis by affecting macrophage function J. Leukoc. Biol., August 1, 2009; 86(2): 361 - 370. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-O. Ahn, J.-C. Lee, M.-W. Sung, and D. S. Heo Presence of Membrane-Bound TGF-{beta}1 and Its Regulation by IL-2-Activated Immune Cell-Derived IFN-{gamma} in Head and Neck Squamous Cell Carcinoma Cell Lines J. Immunol., May 15, 2009; 182(10): 6114 - 6120. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Hagemann, S. K. Biswas, T. Lawrence, A. Sica, and C. E. Lewis Regulation of macrophage function in tumors: the multifaceted role of NF-{kappa}B Blood, April 2, 2009; 113(14): 3139 - 3146. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. S. Ojalvo, W. King, D. Cox, and J. W. Pollard High-Density Gene Expression Analysis of Tumor-Associated Macrophages from Mouse Mammary Tumors Am. J. Pathol., March 1, 2009; 174(3): 1048 - 1064. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Quante and T. C. Wang Inflammation and Stem Cells in Gastrointestinal Carcinogenesis Physiology, December 1, 2008; 23(6): 350 - 359. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Coleman, B. E. Rendon, M. Zhao, M.-W. Qian, R. Bucala, D. Xin, and R. A. Mitchell Cooperative Regulation of Non-Small Cell Lung Carcinoma Angiogenic Potential by Macrophage Migration Inhibitory Factor and Its Homolog, D-Dopachrome Tautomerase J. Immunol., August 15, 2008; 181(4): 2330 - 2337. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Huang, Z. Lei, G.-M. Zhang, D. Li, C. Song, B. Li, Y. Liu, Y. Yuan, J. Unkeless, H. Xiong, et al. SCF-mediated mast cell infiltration and activation exacerbate the inflammation and immunosuppression in tumor microenvironment Blood, August 15, 2008; 112(4): 1269 - 1279. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Hagemann, T. Lawrence, I. McNeish, K. A. Charles, H. Kulbe, R. G. Thompson, S. C. Robinson, and F. R. Balkwill "Re-educating" tumor-associated macrophages by targeting NF-{kappa}B J. Exp. Med., June 9, 2008; 205(6): 1261 - 1268. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Guruvayoorappan Tumor Versus Tumor-Associated Macrophages: How Hot is the Link? Integr Cancer Ther, June 1, 2008; 7(2): 90 - 95. [Abstract] [PDF]
|
|
|
|
|
|
M. E. Armstrong, M. Gantier, L. Li, W. Y. Chung, A. McCann, J. A. Baugh, and S. C. Donnelly Small Interfering RNAs Induce Macrophage Migration Inhibitory Factor Production and Proliferation in Breast Cancer Cells via a Double-Stranded RNA-Dependent Protein Kinase-Dependent Mechanism J. Immunol., June 1, 2008; 180(11): 7125 - 7133. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Till, P. Rosenstiel, K. Brautigam, C. Sina, G. Jacobs, H.-H. Oberg, D. Seegert, T. Chakraborty, and S. Schreiber A role for membrane-bound CD147 in NOD2-mediated recognition of bacterial cytoinvasion J. Cell Sci., February 15, 2008; 121(4): 487 - 495. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Braunstein, S. C. Formenti, and R. J. Schneider Acquisition of Stable Inducible Up-Regulation of Nuclear Factor-{kappa}B by Tumor Necrosis Factor Exposure Confers Increased Radiation Resistance without Increased Transformation in Breast Cancer Cells Mol. Cancer Res., January 1, 2008; 6(1): 78 - 88. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Hagemann, S. C. Robinson, R. G. Thompson, K. Charles, H. Kulbe, and F. R. Balkwill Ovarian cancer cell-derived migration inhibitory factor enhances tumor growth, progression, and angiogenesis Mol. Cancer Ther., July 1, 2007; 6(7): 1993 - 2002. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. M. Robinson-Smith, I. Isaacsohn, C. A. Mercer, M. Zhou, N. Van Rooijen, N. Husseinzadeh, M. M. McFarland-Mancini, and A. F. Drew Macrophages Mediate Inflammation-Enhanced Metastasis of Ovarian Tumors in Mice Cancer Res., June 15, 2007; 67(12): 5708 - 5716. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Cheng, D.-H. Huo, D.-M. Kuang, J. Yang, L. Zheng, and S.-M. Zhuang Human Macrophages Promote the Motility and Invasiveness of Osteopontin-Knockdown Tumor Cells Cancer Res., June 1, 2007; 67(11): 5141 - 5147. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kulbe, R. Thompson, J. L. Wilson, S. Robinson, T. Hagemann, R. Fatah, D. Gould, A. Ayhan, and F. Balkwill The Inflammatory Cytokine Tumor Necrosis Factor-{alpha} Generates an Autocrine Tumor-Promoting Network in Epithelial Ovarian Cancer Cells Cancer Res., January 15, 2007; 67(2): 585 - 592. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Loewe, T. Valero, S. Kremling, B. Pratscher, R. Kunstfeld, H. Pehamberger, and P. Petzelbauer Dimethylfumarate Impairs Melanoma Growth and Metastasis Cancer Res., December 15, 2006; 66(24): 11888 - 11896. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. James, J. H. Lee, and A. J. Klingelhutz Human Papillomavirus Type 16 E6 Activates NF-{kappa}B, Induces cIAP-2 Expression, and Protects against Apoptosis in a PDZ Binding Motif-Dependent Manner. J. Virol., June 1, 2006; 80(11): 5301 - 5307. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Hagemann, J. Wilson, F. Burke, H. Kulbe, N. F. Li, A. Pluddemann, K. Charles, S. Gordon, and F. R. Balkwill Ovarian cancer cells polarize macrophages toward a tumor-associated phenotype. J. Immunol., April 15, 2006; 176(8): 5023 - 5032. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Pukrop, F. Klemm, Th. Hagemann, D. Gradl, M. Schulz, S. Siemes, L. Trumper, and C. Binder Wnt 5a signaling is critical for macrophage-induced invasion of breast cancer cell lines PNAS, April 4, 2006; 103(14): 5454 - 5459. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. F. Basil, Y. Zhao, K. Zavaglia, P. Jin, M. C. Panelli, S. Voiculescu, S. Mandruzzato, H. M. Lee, B. Seliger, R. S. Freedman, et al. Common cancer biomarkers. Cancer Res., March 15, 2006; 66(6): 2953 - 2961. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. E. Lewis and J. W. Pollard Distinct Role of Macrophages in Different Tumor Microenvironments Cancer Res., January 15, 2006; 66(2): 605 - 612. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kulbe, T. Hagemann, P. W. Szlosarek, F. R. Balkwill, and J. L. Wilson The Inflammatory Cytokine Tumor Necrosis Factor-{alpha} Regulates Chemokine Receptor Expression on Ovarian Cancer Cells Cancer Res., November 15, 2005; 65(22): 10355 - 10362. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
