Pancreatic stromal Gremlin 1 expression during pancreatic tumorigenesis
Chronic pancreatitis (CP) is a major risk factor of pancreatic ductal adenocarcinoma (PDAC). How CP promotes pancreatic oncogenesis remains unclear. A characteristic feature of PDAC is its prominent desmoplasia in the tumor microenvironment, composed of activated fibroblasts and macrophages. Macroph...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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KeAi Communications Co., Ltd.
2022-01-01
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| Series: | Genes and Diseases |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352304220300660 |
| _version_ | 1797719580399894528 |
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| author | Joy M. Davis Binglu Cheng Madeline M. Drake Qiang Yu Baibing Yang Jing Li Chunhui Liu Mamoun Younes Xiurong Zhao Jennifer M. Bailey Qiang Shen Tien C. Ko Yanna Cao |
| author_facet | Joy M. Davis Binglu Cheng Madeline M. Drake Qiang Yu Baibing Yang Jing Li Chunhui Liu Mamoun Younes Xiurong Zhao Jennifer M. Bailey Qiang Shen Tien C. Ko Yanna Cao |
| author_sort | Joy M. Davis |
| collection | DOAJ |
| description | Chronic pancreatitis (CP) is a major risk factor of pancreatic ductal adenocarcinoma (PDAC). How CP promotes pancreatic oncogenesis remains unclear. A characteristic feature of PDAC is its prominent desmoplasia in the tumor microenvironment, composed of activated fibroblasts and macrophages. Macrophages can be characterized as M1 or M2, with tumor-inhibiting or -promoting functions, respectively. We reported that Gremlin 1 (GREM1), a key pro-fibrogenic factor, is upregulated in the stroma of CP. The current study aimed to investigate the expression of GREM1 and correlation between GREM1 and macrophages within the pancreas during chronic inflammation and the development of PDAC. By mRNA in situ hybridization, we detected GREM1 mRNA expression within α-smooth muscle actin (SMA)-positive fibroblasts of the pancreatic stroma. These designated FibroblastsGrem1+ marginally increased from CP to pancreatic intraepithelial neoplasia (PanIN) and PDAC. Within PDAC, FibroblastsGrem1+ increased with higher pathological tumor stages and in a majority of PDAC subtypes screened. Additionally, FibroblastsGrem1+ positively correlated with total macrophages (MacCD68+) and M2 macrophages (M2CD163+) in PDAC. To begin exploring potential molecular links between FibroblastsGrem1+ and macrophages in PDAC, we examined the expression of macrophage migration inhibitory factor (MIF), an endogenous counteracting molecule of GREM1 and an M1 macrophage promoting factor. By IHC staining of MIF, we found MIF to be expressed by tumor cells, positively correlated with GREM1; by IHC co-staining, we found MIF to be negatively correlated with M2CD163+ expression. Our findings suggest that GREM1 expression by activated fibroblasts may promote PDAC development, and GREM1/MIF may play an important role in macrophage phenotype. |
| first_indexed | 2024-03-12T09:08:05Z |
| format | Article |
| id | doaj.art-94e40cedec3044679e7cad005c71378b |
| institution | Directory Open Access Journal |
| issn | 2352-3042 |
| language | English |
| last_indexed | 2024-03-12T09:08:05Z |
| publishDate | 2022-01-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Genes and Diseases |
| spelling | doaj.art-94e40cedec3044679e7cad005c71378b2023-09-02T15:13:18ZengKeAi Communications Co., Ltd.Genes and Diseases2352-30422022-01-0191108115Pancreatic stromal Gremlin 1 expression during pancreatic tumorigenesisJoy M. Davis0Binglu Cheng1Madeline M. Drake2Qiang Yu3Baibing Yang4Jing Li5Chunhui Liu6Mamoun Younes7Xiurong Zhao8Jennifer M. Bailey9Qiang Shen10Tien C. Ko11Yanna Cao12Department of Surgery, The University of Texas Health Science Center at Houston, Houston, TX 77030, USADepartment of Surgery, The University of Texas Health Science Center at Houston, Houston, TX 77030, USADepartment of Surgery, The University of Texas Health Science Center at Houston, Houston, TX 77030, USADepartment of Surgery, The University of Texas Health Science Center at Houston, Houston, TX 77030, USADepartment of Surgery, The University of Texas Health Science Center at Houston, Houston, TX 77030, USADepartment of Surgery, The University of Texas Health Science Center at Houston, Houston, TX 77030, USADepartment of Surgery, The University of Texas Health Science Center at Houston, Houston, TX 77030, USADepartment of Pathology & Laboratory Medicine, The University of Texas Health Science Center at Houston, Houston, TX 77030, USADepartment of Neurology, The University of Texas Health Science Center at Houston, Houston, TX 77030, USADepartment of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, TX 77030, USADepartment of Genetics, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USADepartment of Surgery, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA; Corresponding author. Department of Surgery, The University of Texas Health Science Center at Houston, 5656 Kelly, 30S62008, Houston, TX 77026, USA.Department of Surgery, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA; Corresponding author. Department of Surgery, The University of Texas Health Science Center at Houston, 6431 Fannin St., MSB4.608, Houston, TX 77030, USA.Chronic pancreatitis (CP) is a major risk factor of pancreatic ductal adenocarcinoma (PDAC). How CP promotes pancreatic oncogenesis remains unclear. A characteristic feature of PDAC is its prominent desmoplasia in the tumor microenvironment, composed of activated fibroblasts and macrophages. Macrophages can be characterized as M1 or M2, with tumor-inhibiting or -promoting functions, respectively. We reported that Gremlin 1 (GREM1), a key pro-fibrogenic factor, is upregulated in the stroma of CP. The current study aimed to investigate the expression of GREM1 and correlation between GREM1 and macrophages within the pancreas during chronic inflammation and the development of PDAC. By mRNA in situ hybridization, we detected GREM1 mRNA expression within α-smooth muscle actin (SMA)-positive fibroblasts of the pancreatic stroma. These designated FibroblastsGrem1+ marginally increased from CP to pancreatic intraepithelial neoplasia (PanIN) and PDAC. Within PDAC, FibroblastsGrem1+ increased with higher pathological tumor stages and in a majority of PDAC subtypes screened. Additionally, FibroblastsGrem1+ positively correlated with total macrophages (MacCD68+) and M2 macrophages (M2CD163+) in PDAC. To begin exploring potential molecular links between FibroblastsGrem1+ and macrophages in PDAC, we examined the expression of macrophage migration inhibitory factor (MIF), an endogenous counteracting molecule of GREM1 and an M1 macrophage promoting factor. By IHC staining of MIF, we found MIF to be expressed by tumor cells, positively correlated with GREM1; by IHC co-staining, we found MIF to be negatively correlated with M2CD163+ expression. Our findings suggest that GREM1 expression by activated fibroblasts may promote PDAC development, and GREM1/MIF may play an important role in macrophage phenotype.http://www.sciencedirect.com/science/article/pii/S2352304220300660FibroblastsGremlin 1Macrophage migration inhibitory factorMacrophagesPancreatic ductal adenocarcinoma |
| spellingShingle | Joy M. Davis Binglu Cheng Madeline M. Drake Qiang Yu Baibing Yang Jing Li Chunhui Liu Mamoun Younes Xiurong Zhao Jennifer M. Bailey Qiang Shen Tien C. Ko Yanna Cao Pancreatic stromal Gremlin 1 expression during pancreatic tumorigenesis Genes and Diseases Fibroblasts Gremlin 1 Macrophage migration inhibitory factor Macrophages Pancreatic ductal adenocarcinoma |
| title | Pancreatic stromal Gremlin 1 expression during pancreatic tumorigenesis |
| title_full | Pancreatic stromal Gremlin 1 expression during pancreatic tumorigenesis |
| title_fullStr | Pancreatic stromal Gremlin 1 expression during pancreatic tumorigenesis |
| title_full_unstemmed | Pancreatic stromal Gremlin 1 expression during pancreatic tumorigenesis |
| title_short | Pancreatic stromal Gremlin 1 expression during pancreatic tumorigenesis |
| title_sort | pancreatic stromal gremlin 1 expression during pancreatic tumorigenesis |
| topic | Fibroblasts Gremlin 1 Macrophage migration inhibitory factor Macrophages Pancreatic ductal adenocarcinoma |
| url | http://www.sciencedirect.com/science/article/pii/S2352304220300660 |
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