Promotion of Tumor Growth by ADAMTS4 in Colorectal Cancer: Focused on Macrophages
Background/Aims: ADAMTSs (A disintegrin and metalloprotease domains with thrombospondins motifs) are a family of extracellular proteases that have been related to both oncogenic and tumor-suppressive functions. The aim of the present study was to investigate: 1) the mutation, copy-number alterations...
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| Format: | Article |
| Language: | English |
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Cell Physiol Biochem Press GmbH & Co KG
2018-04-01
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| Series: | Cellular Physiology and Biochemistry |
| Subjects: | |
| Online Access: | https://www.karger.com/Article/FullText/489245 |
| _version_ | 1828849825129431040 |
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| author | Jianjun Chen Yang Luo Yong Zhou Shaolan Qin Yier Qiu Ran Cui Minhao Yu Jun Qin Ming Zhong |
| author_facet | Jianjun Chen Yang Luo Yong Zhou Shaolan Qin Yier Qiu Ran Cui Minhao Yu Jun Qin Ming Zhong |
| author_sort | Jianjun Chen |
| collection | DOAJ |
| description | Background/Aims: ADAMTSs (A disintegrin and metalloprotease domains with thrombospondins motifs) are a family of extracellular proteases that have been related to both oncogenic and tumor-suppressive functions. The aim of the present study was to investigate: 1) the mutation, copy-number alterations, and expression profile of ADAMTSs in colorectal cancer and 2) whether ADAMTSs participate in colorectal cancer (CRC) progression and invasion. Methods: The mutation, copy-number alterations, and expression profile of ADAMTSs in CRC were analyzed in the TCGA cohort using cBioportal. ADAMTS4 expression in tumor tissues and cell lines were determined by immunostaining and real-time quantitative PCR. The role of ADAMTS-4 in CRC progression and the underlying mechanisms were studied by using short hairpin RNA-mediated knockdown of ADAMTS4. The effects of ADAMTS4 in cell proliferation and invasion were determined by clone formation assay and transwell migration assay, respectively. Macrophages were depleted by liposomal clodronate in immune-competent BALB/c mice and tumor growth was analyzed. Results: ADAMTS4 was differentially expressed in CRC and predicted a poor prognosis. Elevated ADAMTS4 expression was closely associated with larger tumor size, enhanced TNM stage, and a poor clinical outcome in patients with CRC. ADAMTS4 knockdown had no inhibitory implications on cell proliferation and invasion in vitro, but significantly attenuated tumor growth in vivo. Mechanistically, we revealed that ADAMTS4 was associated macrophages infiltration and polarization in the tumor microenvironment of CRC. Macrophage depletion largely abolished the promotive effect of ADAMTS4 on tumor growth in the immune competent BALB/c mice. Conclusion: ADAMTS4 seemed to be a promising prognostic indicator in CRC. The novel link between ADAMTS4 and macrophages mirrors the potential regulatory roles of ADAMTSs in the inflammatory microenvironment of cancers. |
| first_indexed | 2024-12-12T22:59:29Z |
| format | Article |
| id | doaj.art-a8d97a88ada44b19ad0536bba9186d5d |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-12T22:59:29Z |
| publishDate | 2018-04-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-a8d97a88ada44b19ad0536bba9186d5d2022-12-22T00:08:52ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782018-04-014641693170310.1159/000489245489245Promotion of Tumor Growth by ADAMTS4 in Colorectal Cancer: Focused on MacrophagesJianjun ChenYang LuoYong ZhouShaolan QinYier QiuRan CuiMinhao YuJun QinMing ZhongBackground/Aims: ADAMTSs (A disintegrin and metalloprotease domains with thrombospondins motifs) are a family of extracellular proteases that have been related to both oncogenic and tumor-suppressive functions. The aim of the present study was to investigate: 1) the mutation, copy-number alterations, and expression profile of ADAMTSs in colorectal cancer and 2) whether ADAMTSs participate in colorectal cancer (CRC) progression and invasion. Methods: The mutation, copy-number alterations, and expression profile of ADAMTSs in CRC were analyzed in the TCGA cohort using cBioportal. ADAMTS4 expression in tumor tissues and cell lines were determined by immunostaining and real-time quantitative PCR. The role of ADAMTS-4 in CRC progression and the underlying mechanisms were studied by using short hairpin RNA-mediated knockdown of ADAMTS4. The effects of ADAMTS4 in cell proliferation and invasion were determined by clone formation assay and transwell migration assay, respectively. Macrophages were depleted by liposomal clodronate in immune-competent BALB/c mice and tumor growth was analyzed. Results: ADAMTS4 was differentially expressed in CRC and predicted a poor prognosis. Elevated ADAMTS4 expression was closely associated with larger tumor size, enhanced TNM stage, and a poor clinical outcome in patients with CRC. ADAMTS4 knockdown had no inhibitory implications on cell proliferation and invasion in vitro, but significantly attenuated tumor growth in vivo. Mechanistically, we revealed that ADAMTS4 was associated macrophages infiltration and polarization in the tumor microenvironment of CRC. Macrophage depletion largely abolished the promotive effect of ADAMTS4 on tumor growth in the immune competent BALB/c mice. Conclusion: ADAMTS4 seemed to be a promising prognostic indicator in CRC. The novel link between ADAMTS4 and macrophages mirrors the potential regulatory roles of ADAMTSs in the inflammatory microenvironment of cancers.https://www.karger.com/Article/FullText/489245AdamtssTumor microenvironmentColorectal cancerMacrophages |
| spellingShingle | Jianjun Chen Yang Luo Yong Zhou Shaolan Qin Yier Qiu Ran Cui Minhao Yu Jun Qin Ming Zhong Promotion of Tumor Growth by ADAMTS4 in Colorectal Cancer: Focused on Macrophages Cellular Physiology and Biochemistry Adamtss Tumor microenvironment Colorectal cancer Macrophages |
| title | Promotion of Tumor Growth by ADAMTS4 in Colorectal Cancer: Focused on Macrophages |
| title_full | Promotion of Tumor Growth by ADAMTS4 in Colorectal Cancer: Focused on Macrophages |
| title_fullStr | Promotion of Tumor Growth by ADAMTS4 in Colorectal Cancer: Focused on Macrophages |
| title_full_unstemmed | Promotion of Tumor Growth by ADAMTS4 in Colorectal Cancer: Focused on Macrophages |
| title_short | Promotion of Tumor Growth by ADAMTS4 in Colorectal Cancer: Focused on Macrophages |
| title_sort | promotion of tumor growth by adamts4 in colorectal cancer focused on macrophages |
| topic | Adamtss Tumor microenvironment Colorectal cancer Macrophages |
| url | https://www.karger.com/Article/FullText/489245 |
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