Development of A New Mouse Model for Intrahepatic Cholangiocellular Carcinoma: Accelerating Functions of Pecam-1
Due to the lack of suitable in-vivo models, the etiology of intrahepatic cholangiocellular carcinoma (ICC) is poorly understood. We previously showed the involvement of platelet endothelial cell adhesion molecule-1 (Pecam-1/CD31) in acute liver damage. Here, we developed a model of ICC using thioace...
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MDPI AG
2019-07-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/11/8/1045 |
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| author | Ihtzaz Ahmed Malik Gesa Malik Philipp Ströbel Jörg Wilting |
| author_facet | Ihtzaz Ahmed Malik Gesa Malik Philipp Ströbel Jörg Wilting |
| author_sort | Ihtzaz Ahmed Malik |
| collection | DOAJ |
| description | Due to the lack of suitable in-vivo models, the etiology of intrahepatic cholangiocellular carcinoma (ICC) is poorly understood. We previously showed the involvement of platelet endothelial cell adhesion molecule-1 (Pecam-1/CD31) in acute liver damage. Here, we developed a model of ICC using thioacetamide (TAA) in drinking water of wild-type (WT)-mice and Pecam-1-knock-out (KO)-mice. Gross inspection and microscopy revealed liver-cirrhosis and ICC in both groups after 22 weeks of TAA. The severity of cirrhosis and ICC (Ck-19-positive) was reduced in Pecam-1 KO mice (stage-4 cirrhosis in WT vs. stage-3 in KO mice). Tumor networks (accompanied by neutrophils) were predominantly located in portal areas, with signs of epithelial-to-mesenchymal transition (EMT). In serum, TAA induced an increase in hepatic damage markers, with lower levels in Pecam-1 null mice. With qPCR of liver, elevated expression of Pecam-1 mRNA was noted in WT mice, in addition to Icam-1, EpCam, cytokines, cMyc, and Mmp2. Thereby, levels of EpCAM, cytokines, cMyc, and Mmp2 were significantly lower in Pecam-1 null mice. Lipocalin-2 and Ccl5 were elevated significantly in both WT and Pecam-1 null mice after TAA administration. Also, EMT marker Wnt5a (not Twist-1) was increased in both groups after TAA. We present a highly reproducible mouse model for ICC and show protective effects of Pecam-1 deficiency. |
| first_indexed | 2024-03-12T07:02:38Z |
| format | Article |
| id | doaj.art-d8a58fd49f234b7eb5bfc5685c0c0c33 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T07:02:38Z |
| publishDate | 2019-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-d8a58fd49f234b7eb5bfc5685c0c0c332023-09-02T23:41:49ZengMDPI AGCancers2072-66942019-07-01118104510.3390/cancers11081045cancers11081045Development of A New Mouse Model for Intrahepatic Cholangiocellular Carcinoma: Accelerating Functions of Pecam-1Ihtzaz Ahmed Malik0Gesa Malik1Philipp Ströbel2Jörg Wilting3Department of Anatomy and Cell Biology, University Medical Center Goettingen, Kreuzbergring 36, D-37075 Goettingen, GermanyDepartment of Anatomy and Cell Biology, University Medical Center Goettingen, Kreuzbergring 36, D-37075 Goettingen, GermanyInstitute of Pathology, University Medical Center Goettingen, Robert-Koch-Strasse 40, D-37075 Goettingen, GermanyDepartment of Anatomy and Cell Biology, University Medical Center Goettingen, Kreuzbergring 36, D-37075 Goettingen, GermanyDue to the lack of suitable in-vivo models, the etiology of intrahepatic cholangiocellular carcinoma (ICC) is poorly understood. We previously showed the involvement of platelet endothelial cell adhesion molecule-1 (Pecam-1/CD31) in acute liver damage. Here, we developed a model of ICC using thioacetamide (TAA) in drinking water of wild-type (WT)-mice and Pecam-1-knock-out (KO)-mice. Gross inspection and microscopy revealed liver-cirrhosis and ICC in both groups after 22 weeks of TAA. The severity of cirrhosis and ICC (Ck-19-positive) was reduced in Pecam-1 KO mice (stage-4 cirrhosis in WT vs. stage-3 in KO mice). Tumor networks (accompanied by neutrophils) were predominantly located in portal areas, with signs of epithelial-to-mesenchymal transition (EMT). In serum, TAA induced an increase in hepatic damage markers, with lower levels in Pecam-1 null mice. With qPCR of liver, elevated expression of Pecam-1 mRNA was noted in WT mice, in addition to Icam-1, EpCam, cytokines, cMyc, and Mmp2. Thereby, levels of EpCAM, cytokines, cMyc, and Mmp2 were significantly lower in Pecam-1 null mice. Lipocalin-2 and Ccl5 were elevated significantly in both WT and Pecam-1 null mice after TAA administration. Also, EMT marker Wnt5a (not Twist-1) was increased in both groups after TAA. We present a highly reproducible mouse model for ICC and show protective effects of Pecam-1 deficiency.https://www.mdpi.com/2072-6694/11/8/1045liver cirrhosisinflammationchemokinesbile-duct-cancerproliferationcholangiogenesis |
| spellingShingle | Ihtzaz Ahmed Malik Gesa Malik Philipp Ströbel Jörg Wilting Development of A New Mouse Model for Intrahepatic Cholangiocellular Carcinoma: Accelerating Functions of Pecam-1 Cancers liver cirrhosis inflammation chemokines bile-duct-cancer proliferation cholangiogenesis |
| title | Development of A New Mouse Model for Intrahepatic Cholangiocellular Carcinoma: Accelerating Functions of Pecam-1 |
| title_full | Development of A New Mouse Model for Intrahepatic Cholangiocellular Carcinoma: Accelerating Functions of Pecam-1 |
| title_fullStr | Development of A New Mouse Model for Intrahepatic Cholangiocellular Carcinoma: Accelerating Functions of Pecam-1 |
| title_full_unstemmed | Development of A New Mouse Model for Intrahepatic Cholangiocellular Carcinoma: Accelerating Functions of Pecam-1 |
| title_short | Development of A New Mouse Model for Intrahepatic Cholangiocellular Carcinoma: Accelerating Functions of Pecam-1 |
| title_sort | development of a new mouse model for intrahepatic cholangiocellular carcinoma accelerating functions of pecam 1 |
| topic | liver cirrhosis inflammation chemokines bile-duct-cancer proliferation cholangiogenesis |
| url | https://www.mdpi.com/2072-6694/11/8/1045 |
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