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Recruitment of Myeloid but not Endothelial Precursor Cells Facilitates Tumor Regrowth after Local Irradiation
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| Zeitschriftentitel: | Cancer Research |
|---|---|
| Personen und Körperschaften: | , , , , , |
| In: | Cancer Research, 70, 2010, 14, S. 5679-5685 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Association for Cancer Research (AACR)
|
| Schlagwörter: |
| author_facet |
Kozin, Sergey V. Kamoun, Walid S. Huang, Yuhui Dawson, Michelle R. Jain, Rakesh K. Duda, Dan G. Kozin, Sergey V. Kamoun, Walid S. Huang, Yuhui Dawson, Michelle R. Jain, Rakesh K. Duda, Dan G. |
|---|---|
| author |
Kozin, Sergey V. Kamoun, Walid S. Huang, Yuhui Dawson, Michelle R. Jain, Rakesh K. Duda, Dan G. |
| spellingShingle |
Kozin, Sergey V. Kamoun, Walid S. Huang, Yuhui Dawson, Michelle R. Jain, Rakesh K. Duda, Dan G. Cancer Research Recruitment of Myeloid but not Endothelial Precursor Cells Facilitates Tumor Regrowth after Local Irradiation Cancer Research Oncology |
| author_sort |
kozin, sergey v. |
| spelling |
Kozin, Sergey V. Kamoun, Walid S. Huang, Yuhui Dawson, Michelle R. Jain, Rakesh K. Duda, Dan G. 0008-5472 1538-7445 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/0008-5472.can-09-4446 <jats:title>Abstract</jats:title> <jats:p>Tumor neovascularization and growth might be promoted by the recruitment of bone marrow–derived cells (BMDC), which include endothelial precursor cells and “vascular modulatory” myelomonocytic (CD11b+) cells. BMDCs may also drive tumor regrowth after certain chemotherapeutic and vascular disruption treatments. In this study, we evaluated the role of BMDC recruitment in breast and lung carcinoma xenograft models after local irradiation (LI). We depleted the bone marrow by including whole-body irradiation (WBI) of 6 Gy as part of a total tumor dose of 21 Gy, and compared the growth delay with the one achieved after LI of 21 Gy. In both models, the inclusion of WBI induced longer tumor growth delays. Moreover, WBI increased lung tumor control probability by LI. Exogenous delivery of BMDCs from radiation-naïve donors partially abrogated the WBI effect. Myeloid BMDCs, primarily macrophages, rapidly accumulated in tumors after LI. Intratumoral expression of stromal-derived factor 1α (SDF-1α), a chemokine that promotes tissue retention of BMDCs, was noted 2 days after LI. Conversely, treatment with an inhibitor of SDF-1α receptor CXCR4 (AMD3100) with LI significantly delayed tumor regrowth. However, when administered starting from 5 days post-LI, AMD3100 treatment was ineffective. Lastly, with restorative bone marrow transplantation of Tie2-GFP–labeled BMDC population, we observed an increased number of monocytes but not endothelial precursor cells in tumors that recurred following LI. Our results suggest that an increase in intratumoral SDF-1α triggered by LI recruits myelomonocytes/macrophages which promotes tumor regrowth. Cancer Res; 70(14); 5679–85. ©2010 AACR.</jats:p> Recruitment of Myeloid but not Endothelial Precursor Cells Facilitates Tumor Regrowth after Local Irradiation Cancer Research |
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American Association for Cancer Research (AACR), 2010 |
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0008-5472 1538-7445 |
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| title |
Recruitment of Myeloid but not Endothelial Precursor Cells Facilitates Tumor Regrowth after Local Irradiation |
| title_unstemmed |
Recruitment of Myeloid but not Endothelial Precursor Cells Facilitates Tumor Regrowth after Local Irradiation |
| title_full |
Recruitment of Myeloid but not Endothelial Precursor Cells Facilitates Tumor Regrowth after Local Irradiation |
| title_fullStr |
Recruitment of Myeloid but not Endothelial Precursor Cells Facilitates Tumor Regrowth after Local Irradiation |
| title_full_unstemmed |
Recruitment of Myeloid but not Endothelial Precursor Cells Facilitates Tumor Regrowth after Local Irradiation |
| title_short |
Recruitment of Myeloid but not Endothelial Precursor Cells Facilitates Tumor Regrowth after Local Irradiation |
| title_sort |
recruitment of myeloid but not endothelial precursor cells facilitates tumor regrowth after local irradiation |
| topic |
Cancer Research Oncology |
| url |
http://dx.doi.org/10.1158/0008-5472.can-09-4446 |
| publishDate |
2010 |
| physical |
5679-5685 |
| description |
<jats:title>Abstract</jats:title>
<jats:p>Tumor neovascularization and growth might be promoted by the recruitment of bone marrow–derived cells (BMDC), which include endothelial precursor cells and “vascular modulatory” myelomonocytic (CD11b+) cells. BMDCs may also drive tumor regrowth after certain chemotherapeutic and vascular disruption treatments. In this study, we evaluated the role of BMDC recruitment in breast and lung carcinoma xenograft models after local irradiation (LI). We depleted the bone marrow by including whole-body irradiation (WBI) of 6 Gy as part of a total tumor dose of 21 Gy, and compared the growth delay with the one achieved after LI of 21 Gy. In both models, the inclusion of WBI induced longer tumor growth delays. Moreover, WBI increased lung tumor control probability by LI. Exogenous delivery of BMDCs from radiation-naïve donors partially abrogated the WBI effect. Myeloid BMDCs, primarily macrophages, rapidly accumulated in tumors after LI. Intratumoral expression of stromal-derived factor 1α (SDF-1α), a chemokine that promotes tissue retention of BMDCs, was noted 2 days after LI. Conversely, treatment with an inhibitor of SDF-1α receptor CXCR4 (AMD3100) with LI significantly delayed tumor regrowth. However, when administered starting from 5 days post-LI, AMD3100 treatment was ineffective. Lastly, with restorative bone marrow transplantation of Tie2-GFP–labeled BMDC population, we observed an increased number of monocytes but not endothelial precursor cells in tumors that recurred following LI. Our results suggest that an increase in intratumoral SDF-1α triggered by LI recruits myelomonocytes/macrophages which promotes tumor regrowth. Cancer Res; 70(14); 5679–85. ©2010 AACR.</jats:p> |
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| author | Kozin, Sergey V., Kamoun, Walid S., Huang, Yuhui, Dawson, Michelle R., Jain, Rakesh K., Duda, Dan G. |
| author_facet | Kozin, Sergey V., Kamoun, Walid S., Huang, Yuhui, Dawson, Michelle R., Jain, Rakesh K., Duda, Dan G., Kozin, Sergey V., Kamoun, Walid S., Huang, Yuhui, Dawson, Michelle R., Jain, Rakesh K., Duda, Dan G. |
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| description | <jats:title>Abstract</jats:title> <jats:p>Tumor neovascularization and growth might be promoted by the recruitment of bone marrow–derived cells (BMDC), which include endothelial precursor cells and “vascular modulatory” myelomonocytic (CD11b+) cells. BMDCs may also drive tumor regrowth after certain chemotherapeutic and vascular disruption treatments. In this study, we evaluated the role of BMDC recruitment in breast and lung carcinoma xenograft models after local irradiation (LI). We depleted the bone marrow by including whole-body irradiation (WBI) of 6 Gy as part of a total tumor dose of 21 Gy, and compared the growth delay with the one achieved after LI of 21 Gy. In both models, the inclusion of WBI induced longer tumor growth delays. Moreover, WBI increased lung tumor control probability by LI. Exogenous delivery of BMDCs from radiation-naïve donors partially abrogated the WBI effect. Myeloid BMDCs, primarily macrophages, rapidly accumulated in tumors after LI. Intratumoral expression of stromal-derived factor 1α (SDF-1α), a chemokine that promotes tissue retention of BMDCs, was noted 2 days after LI. Conversely, treatment with an inhibitor of SDF-1α receptor CXCR4 (AMD3100) with LI significantly delayed tumor regrowth. However, when administered starting from 5 days post-LI, AMD3100 treatment was ineffective. Lastly, with restorative bone marrow transplantation of Tie2-GFP–labeled BMDC population, we observed an increased number of monocytes but not endothelial precursor cells in tumors that recurred following LI. Our results suggest that an increase in intratumoral SDF-1α triggered by LI recruits myelomonocytes/macrophages which promotes tumor regrowth. Cancer Res; 70(14); 5679–85. ©2010 AACR.</jats:p> |
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| imprint_str_mv | American Association for Cancer Research (AACR), 2010 |
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| spelling | Kozin, Sergey V. Kamoun, Walid S. Huang, Yuhui Dawson, Michelle R. Jain, Rakesh K. Duda, Dan G. 0008-5472 1538-7445 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/0008-5472.can-09-4446 <jats:title>Abstract</jats:title> <jats:p>Tumor neovascularization and growth might be promoted by the recruitment of bone marrow–derived cells (BMDC), which include endothelial precursor cells and “vascular modulatory” myelomonocytic (CD11b+) cells. BMDCs may also drive tumor regrowth after certain chemotherapeutic and vascular disruption treatments. In this study, we evaluated the role of BMDC recruitment in breast and lung carcinoma xenograft models after local irradiation (LI). We depleted the bone marrow by including whole-body irradiation (WBI) of 6 Gy as part of a total tumor dose of 21 Gy, and compared the growth delay with the one achieved after LI of 21 Gy. In both models, the inclusion of WBI induced longer tumor growth delays. Moreover, WBI increased lung tumor control probability by LI. Exogenous delivery of BMDCs from radiation-naïve donors partially abrogated the WBI effect. Myeloid BMDCs, primarily macrophages, rapidly accumulated in tumors after LI. Intratumoral expression of stromal-derived factor 1α (SDF-1α), a chemokine that promotes tissue retention of BMDCs, was noted 2 days after LI. Conversely, treatment with an inhibitor of SDF-1α receptor CXCR4 (AMD3100) with LI significantly delayed tumor regrowth. However, when administered starting from 5 days post-LI, AMD3100 treatment was ineffective. Lastly, with restorative bone marrow transplantation of Tie2-GFP–labeled BMDC population, we observed an increased number of monocytes but not endothelial precursor cells in tumors that recurred following LI. Our results suggest that an increase in intratumoral SDF-1α triggered by LI recruits myelomonocytes/macrophages which promotes tumor regrowth. Cancer Res; 70(14); 5679–85. ©2010 AACR.</jats:p> Recruitment of Myeloid but not Endothelial Precursor Cells Facilitates Tumor Regrowth after Local Irradiation Cancer Research |
| spellingShingle | Kozin, Sergey V., Kamoun, Walid S., Huang, Yuhui, Dawson, Michelle R., Jain, Rakesh K., Duda, Dan G., Cancer Research, Recruitment of Myeloid but not Endothelial Precursor Cells Facilitates Tumor Regrowth after Local Irradiation, Cancer Research, Oncology |
| title | Recruitment of Myeloid but not Endothelial Precursor Cells Facilitates Tumor Regrowth after Local Irradiation |
| title_full | Recruitment of Myeloid but not Endothelial Precursor Cells Facilitates Tumor Regrowth after Local Irradiation |
| title_fullStr | Recruitment of Myeloid but not Endothelial Precursor Cells Facilitates Tumor Regrowth after Local Irradiation |
| title_full_unstemmed | Recruitment of Myeloid but not Endothelial Precursor Cells Facilitates Tumor Regrowth after Local Irradiation |
| title_short | Recruitment of Myeloid but not Endothelial Precursor Cells Facilitates Tumor Regrowth after Local Irradiation |
| title_sort | recruitment of myeloid but not endothelial precursor cells facilitates tumor regrowth after local irradiation |
| title_unstemmed | Recruitment of Myeloid but not Endothelial Precursor Cells Facilitates Tumor Regrowth after Local Irradiation |
| topic | Cancer Research, Oncology |
| url | http://dx.doi.org/10.1158/0008-5472.can-09-4446 |