Interactions of the chemokines CXCL11 and CXCL12 in human tumor cells
Abstract Background The chemokines, CXCL12 and CXCL11, are upregulated in tumors from many organs and control their progression. CXCL12 and CXCL11 affect tumor cell functions by either binding their prime receptors, CXCR4 and CXCR3, respectively, and/or CXCR7 as a common second chemokine receptor. I...
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| Format: | Article |
| Language: | English |
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BMC
2022-12-01
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| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12885-022-10451-4 |
| _version_ | 1828716741872582656 |
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| author | Christian Koch Nina Charlotte Fischer Malte Puchert Jürgen Engele |
| author_facet | Christian Koch Nina Charlotte Fischer Malte Puchert Jürgen Engele |
| author_sort | Christian Koch |
| collection | DOAJ |
| description | Abstract Background The chemokines, CXCL12 and CXCL11, are upregulated in tumors from many organs and control their progression. CXCL12 and CXCL11 affect tumor cell functions by either binding their prime receptors, CXCR4 and CXCR3, respectively, and/or CXCR7 as a common second chemokine receptor. In humans, CXCR3 exists in the functional splice variants, CXCR3A and CXCR3B, which either have pro- or anti-tumor activity, respectively. Despite the intimate crosstalk between the CXCL12- and CXCL11-system, the impact of a combination of CXCL12 and CXCL11 on tumor progression remains vague. Methods In the present work, we have analyzed CXCL12 and CXCL11 for combined effects on migration, invasion, proliferation, and cytostatic-induced apoptosis of the human tumor cells, A549, A767, A772, DLD-1, and MDA-MB-231. Results We demonstrate that the mode of interaction differs with respect to cell type and function and allows for either potentiation, attenuation or no changes of cellular responses. The divergent responses are not the result of the distinct use of different CXCL12- and CXCL11-receptors by the respective tumor cells, but in case of cell migration seem to be associated with the activation of p38 signaling pathways. Conclusions Our findings point to therapeutic limitations of ongoing efforts to selectively target CXCR3, CXCR4, or CXCR7 in cancer patients, and rather favor individualized targeting strategies. |
| first_indexed | 2024-03-12T14:16:53Z |
| format | Article |
| id | doaj.art-c6ae4b52226745b79fcc4bf3beea9fc9 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-03-12T14:16:53Z |
| publishDate | 2022-12-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-c6ae4b52226745b79fcc4bf3beea9fc92023-08-20T11:13:43ZengBMCBMC Cancer1471-24072022-12-0122111210.1186/s12885-022-10451-4Interactions of the chemokines CXCL11 and CXCL12 in human tumor cellsChristian Koch0Nina Charlotte Fischer1Malte Puchert2Jürgen Engele3Institute of Anatomy, University of Leipzig, Medical FacultyInstitute of Anatomy, University of Leipzig, Medical FacultyInstitute of Anatomy, University of Leipzig, Medical FacultyInstitute of Anatomy, University of Leipzig, Medical FacultyAbstract Background The chemokines, CXCL12 and CXCL11, are upregulated in tumors from many organs and control their progression. CXCL12 and CXCL11 affect tumor cell functions by either binding their prime receptors, CXCR4 and CXCR3, respectively, and/or CXCR7 as a common second chemokine receptor. In humans, CXCR3 exists in the functional splice variants, CXCR3A and CXCR3B, which either have pro- or anti-tumor activity, respectively. Despite the intimate crosstalk between the CXCL12- and CXCL11-system, the impact of a combination of CXCL12 and CXCL11 on tumor progression remains vague. Methods In the present work, we have analyzed CXCL12 and CXCL11 for combined effects on migration, invasion, proliferation, and cytostatic-induced apoptosis of the human tumor cells, A549, A767, A772, DLD-1, and MDA-MB-231. Results We demonstrate that the mode of interaction differs with respect to cell type and function and allows for either potentiation, attenuation or no changes of cellular responses. The divergent responses are not the result of the distinct use of different CXCL12- and CXCL11-receptors by the respective tumor cells, but in case of cell migration seem to be associated with the activation of p38 signaling pathways. Conclusions Our findings point to therapeutic limitations of ongoing efforts to selectively target CXCR3, CXCR4, or CXCR7 in cancer patients, and rather favor individualized targeting strategies.https://doi.org/10.1186/s12885-022-10451-4Chemokine receptorsCXCR4CXCR7CXCR3CXCL11CXCL12 |
| spellingShingle | Christian Koch Nina Charlotte Fischer Malte Puchert Jürgen Engele Interactions of the chemokines CXCL11 and CXCL12 in human tumor cells BMC Cancer Chemokine receptors CXCR4 CXCR7 CXCR3 CXCL11 CXCL12 |
| title | Interactions of the chemokines CXCL11 and CXCL12 in human tumor cells |
| title_full | Interactions of the chemokines CXCL11 and CXCL12 in human tumor cells |
| title_fullStr | Interactions of the chemokines CXCL11 and CXCL12 in human tumor cells |
| title_full_unstemmed | Interactions of the chemokines CXCL11 and CXCL12 in human tumor cells |
| title_short | Interactions of the chemokines CXCL11 and CXCL12 in human tumor cells |
| title_sort | interactions of the chemokines cxcl11 and cxcl12 in human tumor cells |
| topic | Chemokine receptors CXCR4 CXCR7 CXCR3 CXCL11 CXCL12 |
| url | https://doi.org/10.1186/s12885-022-10451-4 |
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