Type IV Collagen in Human Colorectal Liver Metastases—Cellular Origin and a Circulating Biomarker
Circulating type IV collagen (cCOL IV) is a potential biomarker for patients with colorectal liver metastases (CLM) who present with elevated levels of COL IV in both CLM tissue and circulation. This study aimed to establish the cellular origin of elevated levels of COL IV and analyze circulating CO...
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MDPI AG
2022-07-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/14/3396 |
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| author | Moa Lindgren Gunilla Rask Josefin Jonsson Anette Berglund Christina Lundin Pär Jonsson Ingrid Ljuslinder Hanna Nyström |
| author_facet | Moa Lindgren Gunilla Rask Josefin Jonsson Anette Berglund Christina Lundin Pär Jonsson Ingrid Ljuslinder Hanna Nyström |
| author_sort | Moa Lindgren |
| collection | DOAJ |
| description | Circulating type IV collagen (cCOL IV) is a potential biomarker for patients with colorectal liver metastases (CLM) who present with elevated levels of COL IV in both CLM tissue and circulation. This study aimed to establish the cellular origin of elevated levels of COL IV and analyze circulating COL IV in CLM patients. The cellular source was established through in situ hybridization, immunohistochemical staining, and morphological evaluation. Cellular expression in vitro was assessed by immunofluorescence. Tissue expression of COL IV-degrading matrix metalloproteinases (MMPs)-2, -7, -9, and -13 was studied with immunohistochemical staining. Plasma levels of COL IV in CLM patients and healthy controls were analyzed with ELISA. This study shows that cancer-associated fibroblasts (CAFs) express COL IV in the stroma of CLM and that COL IV is expressed in vitro by fibroblasts but not by tumor cells. MMP-2, -7, -9, and -13 are expressed in CLM tissue, mainly by hepatocytes and immune cells, and circulating COL IV is significantly elevated in CLM patients compared with healthy controls. Our study shows that stromal cells, not tumor cells, produce COL IV in CLM, and that circulating COL IV is elevated in patients with CLM. |
| first_indexed | 2024-03-09T03:36:18Z |
| format | Article |
| id | doaj.art-400937262afb40f09be45a490af0cbeb |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T03:36:18Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-400937262afb40f09be45a490af0cbeb2023-12-03T14:47:26ZengMDPI AGCancers2072-66942022-07-011414339610.3390/cancers14143396Type IV Collagen in Human Colorectal Liver Metastases—Cellular Origin and a Circulating BiomarkerMoa Lindgren0Gunilla Rask1Josefin Jonsson2Anette Berglund3Christina Lundin4Pär Jonsson5Ingrid Ljuslinder6Hanna Nyström7Department of Surgical and Perioperative Sciences/Surgery, Umeå University, SE-901 85 Umeå, SwedenDepartment of Surgical and Perioperative Sciences/Surgery, Umeå University, SE-901 85 Umeå, SwedenDepartment of Surgical and Perioperative Sciences/Surgery, Umeå University, SE-901 85 Umeå, SwedenDepartment of Surgical and Perioperative Sciences/Surgery, Umeå University, SE-901 85 Umeå, SwedenDepartment of Surgical and Perioperative Sciences/Surgery, Umeå University, SE-901 85 Umeå, SwedenDepartment of Chemistry, Umeå University, SE-907 36 Umeå, SwedenDepartment of Radiation Sciences/Oncology, Umeå University, SE-901 87 Umeå, SwedenDepartment of Surgical and Perioperative Sciences/Surgery, Umeå University, SE-901 85 Umeå, SwedenCirculating type IV collagen (cCOL IV) is a potential biomarker for patients with colorectal liver metastases (CLM) who present with elevated levels of COL IV in both CLM tissue and circulation. This study aimed to establish the cellular origin of elevated levels of COL IV and analyze circulating COL IV in CLM patients. The cellular source was established through in situ hybridization, immunohistochemical staining, and morphological evaluation. Cellular expression in vitro was assessed by immunofluorescence. Tissue expression of COL IV-degrading matrix metalloproteinases (MMPs)-2, -7, -9, and -13 was studied with immunohistochemical staining. Plasma levels of COL IV in CLM patients and healthy controls were analyzed with ELISA. This study shows that cancer-associated fibroblasts (CAFs) express COL IV in the stroma of CLM and that COL IV is expressed in vitro by fibroblasts but not by tumor cells. MMP-2, -7, -9, and -13 are expressed in CLM tissue, mainly by hepatocytes and immune cells, and circulating COL IV is significantly elevated in CLM patients compared with healthy controls. Our study shows that stromal cells, not tumor cells, produce COL IV in CLM, and that circulating COL IV is elevated in patients with CLM.https://www.mdpi.com/2072-6694/14/14/3396type IV collagenCOL IVcolorectal cancerliver metastasescirculating biomarkerstumor stroma |
| spellingShingle | Moa Lindgren Gunilla Rask Josefin Jonsson Anette Berglund Christina Lundin Pär Jonsson Ingrid Ljuslinder Hanna Nyström Type IV Collagen in Human Colorectal Liver Metastases—Cellular Origin and a Circulating Biomarker Cancers type IV collagen COL IV colorectal cancer liver metastases circulating biomarkers tumor stroma |
| title | Type IV Collagen in Human Colorectal Liver Metastases—Cellular Origin and a Circulating Biomarker |
| title_full | Type IV Collagen in Human Colorectal Liver Metastases—Cellular Origin and a Circulating Biomarker |
| title_fullStr | Type IV Collagen in Human Colorectal Liver Metastases—Cellular Origin and a Circulating Biomarker |
| title_full_unstemmed | Type IV Collagen in Human Colorectal Liver Metastases—Cellular Origin and a Circulating Biomarker |
| title_short | Type IV Collagen in Human Colorectal Liver Metastases—Cellular Origin and a Circulating Biomarker |
| title_sort | type iv collagen in human colorectal liver metastases cellular origin and a circulating biomarker |
| topic | type IV collagen COL IV colorectal cancer liver metastases circulating biomarkers tumor stroma |
| url | https://www.mdpi.com/2072-6694/14/14/3396 |
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