Abstract 2677: Role of CLEC4D in inflammation-driven liver carcinogenesis
| العنوان: | Abstract 2677: Role of CLEC4D in inflammation-driven liver carcinogenesis |
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| المؤلفون: | Elena Riboldi, Chiara Raggi, Elisa Forti, Antonio Sica, Simone Merlin, Nausicaa Clemente, Antonia Follenzi, Fabio Pasqualini, Luca Di Tommaso |
| المصدر: | Cancer Research. 77:2677-2677 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Cancer Research, Tumor microenvironment, Tissue microarray, Stromal cell, business.industry, Inflammation, medicine.disease, Pathogenesis, Immune system, Oncology, Fibrosis, Hepatocellular carcinoma, medicine, Cancer research, medicine.symptom, business |
| الوصف: | Hepatocellular carcinoma (HCC) accounts for approximately 90% of all primary liver tumors and is the second most deadly cancer in the world. HCC commonly arises in a chronically damaged liver that contains large amounts of inflammation and fibrosis. Indeed, interactions among hepatocytes, stromal, and inflammatory cells create a complex microenvironment permissive to tumor development. Myeloid cells are crucial players in cancer-related inflammation. From transcriptional profiling of liver myeloid cells, we identified the gene encoding for the C-type lectin receptor CLEC4D as one of the genes upregulated during the inflammatory response that precedes cancer development in a spontaneous model of murine HCC. We hypothesized that CLEC4D may be involved in the molecular mechanisms that drive HCC pathogenesis. We used the murine model of diethylnitrosamine (DEN)-induced liver carcinogenesis and evaluated tumor growth in genetically modified mice lacking CLEC4D (CLEC4D KO mice), as compared to C57BL/6 wild type (WT) mice. We observed that tumor burden (number of tumors per mouse and tumor dimensions) was reduced in CLEC4D KO mice compared to WT mice. Gene expression analysis of tumor lesions showed that the tumor microenvironment of CLEC4D KO mice was less inflammatory. CLEC4D expression was then evaluated in surgical specimens and tissue microarrays from HCV+ HCC patients. CLEC4D-positive inflammatory cells (macrophages and granulocytes) were present both in the peritumor and in the tumor areas. The percentage of intratumor CLEC4D-positive cells inversely correlated with the degree of the lesion: CLEC4D expression was higher in dysplastic nodules compared to high grade HCCs. Our results indicate that the CLEC4D-dependent pathway contributes to the initiation and the progression of HCC. By targeting CLEC4D, we could modulate immune responses and provide an environment less favorable to tumor growth. An intervention at this level could represent a chemopreventive strategy to arrest the development of HCC in a cirrhotic liver.This work has been supported by Fondazione Cariplo, grant n° 2014-0962. Citation Format: Elena Riboldi, Luca Di Tommaso, Nausicaa Clemente, Chiara Raggi, Elisa Forti, Simone Merlin, Fabio Pasqualini, Antonia Follenzi, Antonio Sica. Role of CLEC4D in inflammation-driven liver carcinogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2677. doi:10.1158/1538-7445.AM2017-2677 |
| تدمد: | 1538-7445 0008-5472 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::78c6526d7a53b6f64b5127b0f929690d https://doi.org/10.1158/1538-7445.am2017-2677 |
| رقم الأكسشن: | edsair.doi...........78c6526d7a53b6f64b5127b0f929690d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15387445 00085472 |
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