Human colorectal cancer-derived carcinoma associated fibroblasts promote CD44-mediated adhesion of colorectal cancer cells to endothelial cells by secretion of HGF
Abstract Background Carcinoma-associated fibroblasts (CAFs) are dominant components of tumor microenvironment, which has been reported to promote development, progression, and metastasis of cancer. However, the role of CAFs during adhesion process remains unknown. It has been hypothesized that CAFs...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-07-01
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| Series: | Cancer Cell International |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12935-019-0914-y |
| _version_ | 1818146842372734976 |
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| author | Rongsheng Zhang Fan Qi Shengli Shao Geng Li Yongdong Feng |
| author_facet | Rongsheng Zhang Fan Qi Shengli Shao Geng Li Yongdong Feng |
| author_sort | Rongsheng Zhang |
| collection | DOAJ |
| description | Abstract Background Carcinoma-associated fibroblasts (CAFs) are dominant components of tumor microenvironment, which has been reported to promote development, progression, and metastasis of cancer. However, the role of CAFs during adhesion process remains unknown. It has been hypothesized that CAFs contribute to adhesion to endothelial cells of colorectal cancer (CRC) via HGF/c-Met pathway. Methods Clinical specimen and orthotopic liver metastasis model was used to investigate association between CD44 expression and propensity of metastasis in CRC. Human CRC derived cancer associated fibroblasts was isolated and its effect on migration and adhesion of CRC cells was investigated. We also confirm the conclusion on animal metastasis model. Results In this study, clinical specimen and orthotopic liver metastatic model indicated that overexpression of CD44 is associated with CRC metastasis, and we found that colorectal cancer-derived CAFs (CC-CAFs) increased the adhesion and migration of CRC cells in vitro through up-regulation of CD44, we also found that CC-CAFs promoted adhesion and liver or lung metastasis in vivo. Mechanistically, we found that the expression of HGF increased tenfolds compared CC-CAFs with adjacent normal fibroblasts, and HGF promoted adhesion through up-regulation of CD44 via HGF/c-MET signal pathway. Conclusions These results indicated that CC-CAFs-derived HGF induced up-regulation of CD44 which mediated adhesion of CRC cells to endothelial cells, and subsequently resulted in enhancement of metastasis of CRC cells, it could provide a novel therapeutic or preventive target. |
| first_indexed | 2024-12-11T12:25:47Z |
| format | Article |
| id | doaj.art-ab4f8ed9059747a0974a37e344a43558 |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-12-11T12:25:47Z |
| publishDate | 2019-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-ab4f8ed9059747a0974a37e344a435582022-12-22T01:07:23ZengBMCCancer Cell International1475-28672019-07-0119111210.1186/s12935-019-0914-yHuman colorectal cancer-derived carcinoma associated fibroblasts promote CD44-mediated adhesion of colorectal cancer cells to endothelial cells by secretion of HGFRongsheng Zhang0Fan Qi1Shengli Shao2Geng Li3Yongdong Feng4Cancer Research Institute, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Otolaryngology-Head and Neck Surgery Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyCancer Research Institute, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyCancer Research Institute, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyCancer Research Institute, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyAbstract Background Carcinoma-associated fibroblasts (CAFs) are dominant components of tumor microenvironment, which has been reported to promote development, progression, and metastasis of cancer. However, the role of CAFs during adhesion process remains unknown. It has been hypothesized that CAFs contribute to adhesion to endothelial cells of colorectal cancer (CRC) via HGF/c-Met pathway. Methods Clinical specimen and orthotopic liver metastasis model was used to investigate association between CD44 expression and propensity of metastasis in CRC. Human CRC derived cancer associated fibroblasts was isolated and its effect on migration and adhesion of CRC cells was investigated. We also confirm the conclusion on animal metastasis model. Results In this study, clinical specimen and orthotopic liver metastatic model indicated that overexpression of CD44 is associated with CRC metastasis, and we found that colorectal cancer-derived CAFs (CC-CAFs) increased the adhesion and migration of CRC cells in vitro through up-regulation of CD44, we also found that CC-CAFs promoted adhesion and liver or lung metastasis in vivo. Mechanistically, we found that the expression of HGF increased tenfolds compared CC-CAFs with adjacent normal fibroblasts, and HGF promoted adhesion through up-regulation of CD44 via HGF/c-MET signal pathway. Conclusions These results indicated that CC-CAFs-derived HGF induced up-regulation of CD44 which mediated adhesion of CRC cells to endothelial cells, and subsequently resulted in enhancement of metastasis of CRC cells, it could provide a novel therapeutic or preventive target.http://link.springer.com/article/10.1186/s12935-019-0914-yColorectal cancerCancer associated fibroblastsAdhesionMetastasis |
| spellingShingle | Rongsheng Zhang Fan Qi Shengli Shao Geng Li Yongdong Feng Human colorectal cancer-derived carcinoma associated fibroblasts promote CD44-mediated adhesion of colorectal cancer cells to endothelial cells by secretion of HGF Cancer Cell International Colorectal cancer Cancer associated fibroblasts Adhesion Metastasis |
| title | Human colorectal cancer-derived carcinoma associated fibroblasts promote CD44-mediated adhesion of colorectal cancer cells to endothelial cells by secretion of HGF |
| title_full | Human colorectal cancer-derived carcinoma associated fibroblasts promote CD44-mediated adhesion of colorectal cancer cells to endothelial cells by secretion of HGF |
| title_fullStr | Human colorectal cancer-derived carcinoma associated fibroblasts promote CD44-mediated adhesion of colorectal cancer cells to endothelial cells by secretion of HGF |
| title_full_unstemmed | Human colorectal cancer-derived carcinoma associated fibroblasts promote CD44-mediated adhesion of colorectal cancer cells to endothelial cells by secretion of HGF |
| title_short | Human colorectal cancer-derived carcinoma associated fibroblasts promote CD44-mediated adhesion of colorectal cancer cells to endothelial cells by secretion of HGF |
| title_sort | human colorectal cancer derived carcinoma associated fibroblasts promote cd44 mediated adhesion of colorectal cancer cells to endothelial cells by secretion of hgf |
| topic | Colorectal cancer Cancer associated fibroblasts Adhesion Metastasis |
| url | http://link.springer.com/article/10.1186/s12935-019-0914-y |
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