Cancer letters, 2020-09, Vol.487, p.53-62
2020
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- Autor(en) / Beteiligte
- Titel
- Disruption of CCR1-mediated myeloid cell accumulation suppresses colorectal cancer progression in mice
- Ist Teil von
- Cancer letters, 2020-09, Vol.487, p.53-62
- Ort / Verlag
- Ireland: Elsevier B.V
- Erscheinungsjahr
- 2020
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Tumor-stromal interaction is implicated in tumor progression. Although CCR1 expression in myeloid cells could be associated with pro-tumor activity, it remains elusive whether disruption of CCR1-mediated myeloid cell accumulation can suppress tumor progression. Here, we investigated the role of CCR1 depletion in myeloid cells in two syngeneic colorectal cancer mouse models: MC38, a transplanted tumor model and CMT93, a liver metastasis model. Both cells induced tumor accumulation of CCR1+ myeloid cells that express MMP2, MMP9, iNOS, and VEGF. Lack of the Ccr1 gene in host mice dramatically reduced MC38 tumor growth as well as CMT93 liver metastasis. To delineate the contribution of CCR1+ myeloid cells, we performed bone marrow (BM) transfer experiments in which sub-lethally irradiated wild-type mice were reconstituted with BM from either wild-type or Ccr1−/− mice. Mice reconstituted with Ccr1−/− BM exhibited marked suppression of MC38 tumor growth and CMT93 liver metastasis, compared with control mice. Consistent with these results, administration of a neutralizing anti-CCR1 monoclonal antibody, KM5908, significantly suppressed MC38 tumor growth and CMT93 liver metastases. Our findings highlight the importance of the application of CCR1 blockade as a therapeutic strategy.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0304-3835eISSN: 1872-7980DOI: 10.1016/j.canlet.2020.05.028Titel-ID: cdi_proquest_miscellaneous_2408198676
- Format
- –
- Schlagworte
- Animal models, Animals, Antibodies, Bone marrow, Bone Marrow - metabolism, Bone Marrow - pathology, CCR1, CCR1 protein, Cell Line, Tumor, Cell- and Tissue-Based Therapy, Chemokines, Cloning, Colorectal cancer, Colorectal carcinoma, Colorectal Neoplasms - genetics, Colorectal Neoplasms - pathology, Colorectal Neoplasms - therapy, Cytokines, Disease Models, Animal, Disease Progression, Drug dosages, Gelatinase A, Gelatinase B, Gene Expression Regulation, Neoplastic - genetics, Hepatocytes, Heterografts, Humans, Liver, Liver Neoplasms - genetics, Liver Neoplasms - pathology, Liver Neoplasms - secondary, Liver Neoplasms - therapy, Matrix Metalloproteinase 2 - genetics, Matrix Metalloproteinase 9 - genetics, Medical research, Metastases, Metastasis, Mice, Monoclonal antibodies, Myeloid cell, Myeloid cells, Myeloid Cells - metabolism, Myeloid Cells - pathology, Neoplasm Metastasis, Neutrophils, Nitric Oxide Synthase Type II - genetics, Nitric-oxide synthase, Protein-Serine-Threonine Kinases - genetics, Protein-Serine-Threonine Kinases - therapeutic use, Software, Spleen, Syngeneic grafts, Tumor microenvironment, Tumors, Vascular endothelial growth factor, Vascular Endothelial Growth Factor A - genetics