Human lung cancer cells express functionally active Toll-like receptor 9
<p>Abstract</p> <p>Background</p> <p>CpG-oligonucleotides (CpG-ODN), which induce signaling through Toll-like receptor 9 (TLR9), are currently under investigation as adjuvants in therapy against infections and cancer. CpG-ODN function as Th-1 adjuvants and are able to a...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2005-01-01
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| Series: | Respiratory Research |
| Online Access: | http://respiratory-research.com/content/6/1/1 |
| _version_ | 1811245011349536768 |
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| author | Vollmer Ekkehard Branscheid Detlev Ulmer Artur J Gerdes Johannes Albrecht Dirk Droemann Daniel Dalhoff Klaus Zabel Peter Goldmann Torsten |
| author_facet | Vollmer Ekkehard Branscheid Detlev Ulmer Artur J Gerdes Johannes Albrecht Dirk Droemann Daniel Dalhoff Klaus Zabel Peter Goldmann Torsten |
| author_sort | Vollmer Ekkehard |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>CpG-oligonucleotides (CpG-ODN), which induce signaling through Toll-like receptor 9 (TLR9), are currently under investigation as adjuvants in therapy against infections and cancer. CpG-ODN function as Th-1 adjuvants and are able to activate dendritic cells. In humans TLR9 has been described to be strongly expressed in B-lymphocytes, monocytes, plasmacytoid dendritic cells and at low levels in human respiratory cells. We determined whether a direct interaction of bacterial DNA with the tumor cells themselves is possible and investigated the expression and function of TLR9 in human malignant solid tumors and cell lines. TLR9 expression by malignant tumor cells, would affect treatment approaches using CpG-ODN on the one hand, and, on the other hand, provide additional novel information about the role of tumor cells in tumor-immunology.</p> <p>Methods</p> <p>The expression of TLR9 in HOPE-fixed non-small lung cancer, non-malignant tissue and tumor cell lines was assessed using immunohistochemistry, confocal microscopy, <it>in situ </it>hybridization, RT-PCR and DNA-sequencing. Apoptosis and chemokine expression was detected by FACS analysis and the Bio-Plex system.</p> <p>Results</p> <p>We found high TLR9 signal intensities in the cytoplasm of tumor cells in the majority of lung cancer specimens as well as in all tested tumor cell lines. In contrast to this non-malignant lung tissues showed only sporadically weak expression. Stimulation of HeLa and A549 cells with CpG-ODN induced secretion of monocyte chemoattractant protein-1 and reduction of spontaneous and tumor necrosis factor-alpha induced apoptosis.</p> <p>Conclusions</p> <p>Here we show that TLR9 is expressed in a selection of human lung cancer tissues and various tumor cell lines. The expression of functionally active TLR9 in human malignant tumors might affect treatment approaches using CpG-ODN and shows that malignant cells can be regarded as active players in tumor-immunology.</p> |
| first_indexed | 2024-04-12T14:33:46Z |
| format | Article |
| id | doaj.art-e3a8922474c841f5aed48c5b7eff8e0b |
| institution | Directory Open Access Journal |
| issn | 1465-9921 |
| language | English |
| last_indexed | 2024-04-12T14:33:46Z |
| publishDate | 2005-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-e3a8922474c841f5aed48c5b7eff8e0b2022-12-22T03:29:10ZengBMCRespiratory Research1465-99212005-01-0161110.1186/1465-9921-6-1Human lung cancer cells express functionally active Toll-like receptor 9Vollmer EkkehardBranscheid DetlevUlmer Artur JGerdes JohannesAlbrecht DirkDroemann DanielDalhoff KlausZabel PeterGoldmann Torsten<p>Abstract</p> <p>Background</p> <p>CpG-oligonucleotides (CpG-ODN), which induce signaling through Toll-like receptor 9 (TLR9), are currently under investigation as adjuvants in therapy against infections and cancer. CpG-ODN function as Th-1 adjuvants and are able to activate dendritic cells. In humans TLR9 has been described to be strongly expressed in B-lymphocytes, monocytes, plasmacytoid dendritic cells and at low levels in human respiratory cells. We determined whether a direct interaction of bacterial DNA with the tumor cells themselves is possible and investigated the expression and function of TLR9 in human malignant solid tumors and cell lines. TLR9 expression by malignant tumor cells, would affect treatment approaches using CpG-ODN on the one hand, and, on the other hand, provide additional novel information about the role of tumor cells in tumor-immunology.</p> <p>Methods</p> <p>The expression of TLR9 in HOPE-fixed non-small lung cancer, non-malignant tissue and tumor cell lines was assessed using immunohistochemistry, confocal microscopy, <it>in situ </it>hybridization, RT-PCR and DNA-sequencing. Apoptosis and chemokine expression was detected by FACS analysis and the Bio-Plex system.</p> <p>Results</p> <p>We found high TLR9 signal intensities in the cytoplasm of tumor cells in the majority of lung cancer specimens as well as in all tested tumor cell lines. In contrast to this non-malignant lung tissues showed only sporadically weak expression. Stimulation of HeLa and A549 cells with CpG-ODN induced secretion of monocyte chemoattractant protein-1 and reduction of spontaneous and tumor necrosis factor-alpha induced apoptosis.</p> <p>Conclusions</p> <p>Here we show that TLR9 is expressed in a selection of human lung cancer tissues and various tumor cell lines. The expression of functionally active TLR9 in human malignant tumors might affect treatment approaches using CpG-ODN and shows that malignant cells can be regarded as active players in tumor-immunology.</p>http://respiratory-research.com/content/6/1/1 |
| spellingShingle | Vollmer Ekkehard Branscheid Detlev Ulmer Artur J Gerdes Johannes Albrecht Dirk Droemann Daniel Dalhoff Klaus Zabel Peter Goldmann Torsten Human lung cancer cells express functionally active Toll-like receptor 9 Respiratory Research |
| title | Human lung cancer cells express functionally active Toll-like receptor 9 |
| title_full | Human lung cancer cells express functionally active Toll-like receptor 9 |
| title_fullStr | Human lung cancer cells express functionally active Toll-like receptor 9 |
| title_full_unstemmed | Human lung cancer cells express functionally active Toll-like receptor 9 |
| title_short | Human lung cancer cells express functionally active Toll-like receptor 9 |
| title_sort | human lung cancer cells express functionally active toll like receptor 9 |
| url | http://respiratory-research.com/content/6/1/1 |
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