The relationship between chemokines CCL2, CCL3, and CCL4 with the tumor microenvironment and tumor-associated macrophage markers in colorectal cancer
A complex network of chemokines can influence cancer progression with the recruitment and activation of hematopoietic cells, including macrophages to the supporting tumor stroma promoting carcinogenesis and metastasis. The aim of this study was to investigate the relation between tissue and plasma c...
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SAGE Publishing
2018-11-01
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| Series: | Tumor Biology |
| Online Access: | https://doi.org/10.1177/1010428318810059 |
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| author | Marjorie De la Fuente López Glauben Landskron Daniela Parada Karen Dubois-Camacho Daniela Simian Maripaz Martinez Diego Romero Juan Carlos Roa Isidora Chahuán Rocío Gutiérrez Francisco Lopez-K Karin Alvarez Udo Kronberg Sebastian López Antonella Sanguinetti Natalia Moreno Mario Abedrapo María-Julieta González Rodrigo Quera Marcela A Hermoso-R |
| author_facet | Marjorie De la Fuente López Glauben Landskron Daniela Parada Karen Dubois-Camacho Daniela Simian Maripaz Martinez Diego Romero Juan Carlos Roa Isidora Chahuán Rocío Gutiérrez Francisco Lopez-K Karin Alvarez Udo Kronberg Sebastian López Antonella Sanguinetti Natalia Moreno Mario Abedrapo María-Julieta González Rodrigo Quera Marcela A Hermoso-R |
| author_sort | Marjorie De la Fuente López |
| collection | DOAJ |
| description | A complex network of chemokines can influence cancer progression with the recruitment and activation of hematopoietic cells, including macrophages to the supporting tumor stroma promoting carcinogenesis and metastasis. The aim of this study was to investigate the relation between tissue and plasma chemokine levels involved in macrophage recruitment with tumor-associated macrophage profile markers and clinicopathological features such as tumor–node–metastases stage, desmoplasia, tumor necrosis factor-α, and vascular endothelial growth factor plasma content. Plasma and tumor/healthy mucosa were obtained from Chilean patients undergoing colon cancer surgery. Chemokines were evaluated from tissue lysates (CCL2, CCL3, CCL4, CCL5, and CX3CL1) by Luminex. Statistical analysis was performed using Wilcoxon match-paired test ( p < 0.05). Macrophage markers (CD68, CD163, and iNOS) were evaluated by immunohistochemistry samples derived from colorectal cancer patients. Correlation analysis between chemokines and macrophage markers and clinicopathological features were performed using Spearman’s test. Plasmatic levels of chemokines and inflammatory mediators’ vascular endothelial growth factor and tumor necrosis factor-α were evaluated by Luminex. Tumor levels of CCL2 (mean ± standard deviation = 530.1 ± 613.9 pg/mg), CCL3 (102.7 ± 106.0 pg/mg), and CCL4 (64.98 ± 48.09 pg/mg) were higher than those found in healthy tissue (182.1 ± 116.5, 26.79 ± 22.40, and 27.06 ± 23.69 pg/mg, respectively p < 0.05). The tumor characterization allowed us to identify a positive correlation between CCL4 and the pro-tumor macrophages marker CD163 ( p = 0.0443), and a negative correlation of iNOS with desmoplastic reaction ( p = 0.0467). Moreover, we identified that tumors with immature desmoplasia have a higher CD163 density compared to those with a mature/intermediated stromal tissue ( p = 0.0288). Plasmatic CCL4 has shown a positive correlation with inflammatory mediators (tumor necrosis factor-α and vascular endothelial growth factor) that have previously been associated with poor prognosis in patients. In conclusion High expression of CCL4 in colon cancer could induce the infiltration of tumor-associated macrophages and specifically a pro-tumor macrophage profile (CD163 + cells). Moreover, plasmatic chemokines could be considered inflammatory mediators associated to CRC progression as well as tumor necrosis factor-α and vascular endothelial growth factor. These data reinforce the idea of chemokines as potential therapeutic targets or biomarker in CRC. |
| format | Article |
| id | doaj-art-00d69d2af1bc4caea79e3f0987683ef0 |
| institution | Kabale University |
| issn | 1423-0380 |
| language | English |
| publishDate | 2018-11-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Tumor Biology |
| spelling | doaj-art-00d69d2af1bc4caea79e3f0987683ef02025-08-20T03:33:14ZengSAGE PublishingTumor Biology1423-03802018-11-014010.1177/1010428318810059The relationship between chemokines CCL2, CCL3, and CCL4 with the tumor microenvironment and tumor-associated macrophage markers in colorectal cancerMarjorie De la Fuente López0Glauben Landskron1Daniela Parada2Karen Dubois-Camacho3Daniela Simian4Maripaz Martinez5Diego Romero6Juan Carlos Roa7Isidora Chahuán8Rocío Gutiérrez9Francisco Lopez-K10Karin Alvarez11Udo Kronberg12Sebastian López13Antonella Sanguinetti14Natalia Moreno15Mario Abedrapo16María-Julieta González17Rodrigo Quera18Marcela A Hermoso-R19Innate Immunity Laboratory, Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago, ChileInnate Immunity Laboratory, Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago, ChileInnate Immunity Laboratory, Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago, ChileInnate Immunity Laboratory, Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago, ChileAcademic Research Unit, Clínica Las Condes, Santiago, ChileAcademic Research Unit, Clínica Las Condes, Santiago, ChileDepartment of Anatomic Pathology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, ChileDepartment of Anatomic Pathology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, ChileInnate Immunity Laboratory, Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago, ChileInnate Immunity Laboratory, Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago, ChileLaboratory of Oncology and Molecular Genetics, Colorectal Surgery Unit, Clínica Las Condes, Santiago, ChileLaboratory of Oncology and Molecular Genetics, Colorectal Surgery Unit, Clínica Las Condes, Santiago, ChileLaboratory of Oncology and Molecular Genetics, Colorectal Surgery Unit, Clínica Las Condes, Santiago, ChileColoproctology Unit, Hospital Clínico Universidad de Chile, Santiago, ChileColoproctology Unit, Hospital Clínico Universidad de Chile, Santiago, ChileColoproctology Unit, Hospital Clínico Universidad de Chile, Santiago, ChileColoproctology Unit, Hospital Clínico Universidad de Chile, Santiago, ChileProgram of Cell Biology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago, ChileGastroenterology Service, Clinica Las Condes, Santiago, ChileInnate Immunity Laboratory, Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago, ChileA complex network of chemokines can influence cancer progression with the recruitment and activation of hematopoietic cells, including macrophages to the supporting tumor stroma promoting carcinogenesis and metastasis. The aim of this study was to investigate the relation between tissue and plasma chemokine levels involved in macrophage recruitment with tumor-associated macrophage profile markers and clinicopathological features such as tumor–node–metastases stage, desmoplasia, tumor necrosis factor-α, and vascular endothelial growth factor plasma content. Plasma and tumor/healthy mucosa were obtained from Chilean patients undergoing colon cancer surgery. Chemokines were evaluated from tissue lysates (CCL2, CCL3, CCL4, CCL5, and CX3CL1) by Luminex. Statistical analysis was performed using Wilcoxon match-paired test ( p < 0.05). Macrophage markers (CD68, CD163, and iNOS) were evaluated by immunohistochemistry samples derived from colorectal cancer patients. Correlation analysis between chemokines and macrophage markers and clinicopathological features were performed using Spearman’s test. Plasmatic levels of chemokines and inflammatory mediators’ vascular endothelial growth factor and tumor necrosis factor-α were evaluated by Luminex. Tumor levels of CCL2 (mean ± standard deviation = 530.1 ± 613.9 pg/mg), CCL3 (102.7 ± 106.0 pg/mg), and CCL4 (64.98 ± 48.09 pg/mg) were higher than those found in healthy tissue (182.1 ± 116.5, 26.79 ± 22.40, and 27.06 ± 23.69 pg/mg, respectively p < 0.05). The tumor characterization allowed us to identify a positive correlation between CCL4 and the pro-tumor macrophages marker CD163 ( p = 0.0443), and a negative correlation of iNOS with desmoplastic reaction ( p = 0.0467). Moreover, we identified that tumors with immature desmoplasia have a higher CD163 density compared to those with a mature/intermediated stromal tissue ( p = 0.0288). Plasmatic CCL4 has shown a positive correlation with inflammatory mediators (tumor necrosis factor-α and vascular endothelial growth factor) that have previously been associated with poor prognosis in patients. In conclusion High expression of CCL4 in colon cancer could induce the infiltration of tumor-associated macrophages and specifically a pro-tumor macrophage profile (CD163 + cells). Moreover, plasmatic chemokines could be considered inflammatory mediators associated to CRC progression as well as tumor necrosis factor-α and vascular endothelial growth factor. These data reinforce the idea of chemokines as potential therapeutic targets or biomarker in CRC.https://doi.org/10.1177/1010428318810059 |
| spellingShingle | Marjorie De la Fuente López Glauben Landskron Daniela Parada Karen Dubois-Camacho Daniela Simian Maripaz Martinez Diego Romero Juan Carlos Roa Isidora Chahuán Rocío Gutiérrez Francisco Lopez-K Karin Alvarez Udo Kronberg Sebastian López Antonella Sanguinetti Natalia Moreno Mario Abedrapo María-Julieta González Rodrigo Quera Marcela A Hermoso-R The relationship between chemokines CCL2, CCL3, and CCL4 with the tumor microenvironment and tumor-associated macrophage markers in colorectal cancer Tumor Biology |
| title | The relationship between chemokines CCL2, CCL3, and CCL4 with the tumor microenvironment and tumor-associated macrophage markers in colorectal cancer |
| title_full | The relationship between chemokines CCL2, CCL3, and CCL4 with the tumor microenvironment and tumor-associated macrophage markers in colorectal cancer |
| title_fullStr | The relationship between chemokines CCL2, CCL3, and CCL4 with the tumor microenvironment and tumor-associated macrophage markers in colorectal cancer |
| title_full_unstemmed | The relationship between chemokines CCL2, CCL3, and CCL4 with the tumor microenvironment and tumor-associated macrophage markers in colorectal cancer |
| title_short | The relationship between chemokines CCL2, CCL3, and CCL4 with the tumor microenvironment and tumor-associated macrophage markers in colorectal cancer |
| title_sort | relationship between chemokines ccl2 ccl3 and ccl4 with the tumor microenvironment and tumor associated macrophage markers in colorectal cancer |
| url | https://doi.org/10.1177/1010428318810059 |
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