Control of Both Myeloid Cell Infiltration and Angiogenesis by CCR1 Promotes Liver Cancer Metastasis Development in Mice
Expression of the CC chemokine receptor 1 (CCR1) by tumor cells has been associated with protumoral activity; however, its role in nontumoral cells during tumor development remains elusive. Here, we investigated the role of CCR1 deletion on stromal and hematopoietic cells in a liver metastasis tumor...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2013-06-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558613801376 |
| _version_ | 1811258031008120832 |
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| author | Mathieu Paul Rodero Constance Auvynet Lucie Poupel Behazine Combadière Christophe Combadière |
| author_facet | Mathieu Paul Rodero Constance Auvynet Lucie Poupel Behazine Combadière Christophe Combadière |
| author_sort | Mathieu Paul Rodero |
| collection | DOAJ |
| description | Expression of the CC chemokine receptor 1 (CCR1) by tumor cells has been associated with protumoral activity; however, its role in nontumoral cells during tumor development remains elusive. Here, we investigated the role of CCR1 deletion on stromal and hematopoietic cells in a liver metastasis tumor model. Metastasis development was strongly impaired in CCR1-deficient mice compared to control mice and was associated with reduced liver monocyte infiltration. To decipher the role of myeloid cells, sublethally irradiated mice were reconstituted with CCR1-deficient bone marrow (BM) and showed better survival rates than the control reconstituted mice. These results point toward the involvement of CCR1 myeloid cell infiltration in the promotion of tumor burden. In addition, survival rates were extended in CCR1-deficient mice receiving either control or CCR1-deficient BM, indicating that host CCR1 expression on nonhematopoietic cells also supports tumor growth. Finally, we found defective tumor-induced neoangiogenesis (in vitro and in vivo) in CCR1-deficient mice. Overall, our results indicate that CCR1 expression by both hematopoietic and nonhematopoietic cells favors tumor aggressiveness. We propose CCR1 as a potential therapeutical target for liver metastasis therapy. |
| first_indexed | 2024-04-12T18:06:56Z |
| format | Article |
| id | doaj.art-17a9cd512ef9463e9b2cc224243f51ba |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-04-12T18:06:56Z |
| publishDate | 2013-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-17a9cd512ef9463e9b2cc224243f51ba2022-12-22T03:21:57ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022013-06-0115664164810.1593/neo.121866Control of Both Myeloid Cell Infiltration and Angiogenesis by CCR1 Promotes Liver Cancer Metastasis Development in MiceMathieu Paul Rodero0Constance Auvynet1Lucie Poupel2Behazine Combadière3Christophe Combadière4Institut National de la Santé et de la Recherche Médicale, (INSERM) UMR-S 945-IUC and Université Pierre et Marie Curie (Paris 6), Laboratory of Immunity and Infection, Institut Universitaire du Cancer, Paris, FranceInstitut National de la Santé et de la Recherche Médicale, (INSERM) UMR-S 945-IUC and Université Pierre et Marie Curie (Paris 6), Laboratory of Immunity and Infection, Institut Universitaire du Cancer, Paris, FranceInstitut National de la Santé et de la Recherche Médicale, (INSERM) UMR-S 945-IUC and Université Pierre et Marie Curie (Paris 6), Laboratory of Immunity and Infection, Institut Universitaire du Cancer, Paris, FranceInstitut National de la Santé et de la Recherche Médicale, (INSERM) UMR-S 945-IUC and Université Pierre et Marie Curie (Paris 6), Laboratory of Immunity and Infection, Institut Universitaire du Cancer, Paris, FranceInstitut National de la Santé et de la Recherche Médicale, (INSERM) UMR-S 945-IUC and Université Pierre et Marie Curie (Paris 6), Laboratory of Immunity and Infection, Institut Universitaire du Cancer, Paris, FranceExpression of the CC chemokine receptor 1 (CCR1) by tumor cells has been associated with protumoral activity; however, its role in nontumoral cells during tumor development remains elusive. Here, we investigated the role of CCR1 deletion on stromal and hematopoietic cells in a liver metastasis tumor model. Metastasis development was strongly impaired in CCR1-deficient mice compared to control mice and was associated with reduced liver monocyte infiltration. To decipher the role of myeloid cells, sublethally irradiated mice were reconstituted with CCR1-deficient bone marrow (BM) and showed better survival rates than the control reconstituted mice. These results point toward the involvement of CCR1 myeloid cell infiltration in the promotion of tumor burden. In addition, survival rates were extended in CCR1-deficient mice receiving either control or CCR1-deficient BM, indicating that host CCR1 expression on nonhematopoietic cells also supports tumor growth. Finally, we found defective tumor-induced neoangiogenesis (in vitro and in vivo) in CCR1-deficient mice. Overall, our results indicate that CCR1 expression by both hematopoietic and nonhematopoietic cells favors tumor aggressiveness. We propose CCR1 as a potential therapeutical target for liver metastasis therapy.http://www.sciencedirect.com/science/article/pii/S1476558613801376 |
| spellingShingle | Mathieu Paul Rodero Constance Auvynet Lucie Poupel Behazine Combadière Christophe Combadière Control of Both Myeloid Cell Infiltration and Angiogenesis by CCR1 Promotes Liver Cancer Metastasis Development in Mice Neoplasia: An International Journal for Oncology Research |
| title | Control of Both Myeloid Cell Infiltration and Angiogenesis by CCR1 Promotes Liver Cancer Metastasis Development in Mice |
| title_full | Control of Both Myeloid Cell Infiltration and Angiogenesis by CCR1 Promotes Liver Cancer Metastasis Development in Mice |
| title_fullStr | Control of Both Myeloid Cell Infiltration and Angiogenesis by CCR1 Promotes Liver Cancer Metastasis Development in Mice |
| title_full_unstemmed | Control of Both Myeloid Cell Infiltration and Angiogenesis by CCR1 Promotes Liver Cancer Metastasis Development in Mice |
| title_short | Control of Both Myeloid Cell Infiltration and Angiogenesis by CCR1 Promotes Liver Cancer Metastasis Development in Mice |
| title_sort | control of both myeloid cell infiltration and angiogenesis by ccr1 promotes liver cancer metastasis development in mice |
| url | http://www.sciencedirect.com/science/article/pii/S1476558613801376 |
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