Lymphatic vessel remodeling and invasion in pancreatic cancer progression
| Autor: | Pankaj J. Pasricha, Yu-Wen Tien, Chi Che Hsieh, Subhash Kulkarni, Yung-Ming Jeng, Mei Hsin Chung, Ya Hsien Chou, Tsai Chen Chiang, King Siang Goh, Chia-Ning Shen, Hung Jen Chien, Chi Ruei Huang, Shih Jung Peng, Shiue-Cheng Tang, Chih Yuan Lee |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Pathology Research paper PDAC pancreatic ductal adenocarcinoma Pancreatic Intraepithelial Neoplasia Fluorescent Antibody Technique Metastasis Pancreatic intraepithelial neoplasia EGFP enhanced green fluorescence protein Pancreatic ductal adenocarcinoma Mice 0302 clinical medicine Tumor Microenvironment EK mice elastase-CreER LSL-KrasG12D mice Lymphatic vessel Lymphangiogenesis 3-D 3-dimensional Lyve1 lymphatic vessel endothelial hyaluronan receptor 1 Neovascularization Pathologic General Medicine p53 mutation medicine.anatomical_structure Lymphatic system 030220 oncology & carcinogenesis Disease Progression Heterografts Pancreas KrasG12D mutation EKP mice elastase-CreER LSL-KrasG12D p53+/− mice medicine.medical_specialty Endothelium Cancer invasion Vascular Remodeling General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Pancreatic cancer medicine Animals Humans Lymphatic Vessels business.industry PanIN pancreatic intraepithelial neoplasia 2-D 2-dimensional medicine.disease Pancreatic Neoplasms Disease Models Animal 030104 developmental biology Lymphovascular invasion H&E hematoxylin and eosin Lymph Nodes business Biomarkers |
| Zdroj: | EBioMedicine |
| ISSN: | 2352-3964 |
| Popis: | Background The lymphatic system is involved in metastasis in pancreatic cancer progression. In cancer staging, lymphatic spread has been used to assess the invasiveness of tumor cells. However, from the endothelium's perspective, the analysis downplays the peri-lesional activities of lymphatic vessels. This unintended bias is largely due to the lack of 3-dimensional (3-D) tissue information to depict the lesion microstructure and vasculature in a global and integrated fashion. Methods We targeted the pancreas as the model organ to investigate lymphatic vessel remodeling in cancer lesion progression. Transparent pancreases were prepared by tissue clearing to facilitate deep-tissue, tile-scanning microscopy for 3-D lymphatic network imaging. Findings In human pancreatic ductal adenocarcinoma, we identify the close association between the pancreatic intraepithelial neoplasia (PanIN) lesions and the lymphatic network. In mouse models of PanIN (elastase-CreER;LSL-KrasG12D and elastase-CreER;LSL-KrasG12D;p53+/-), the 3-D image data reveal the peri-lesional lymphangiogenesis, endothelial invagination, formation of the bridge/valve-like luminal tubules, vasodilation, and luminal invasion. In the orthotopic mouse model of pancreatic cancer, we identify the localized, graft-induced lymphangiogenesis and the peri- and intra-tumoral lymphatic vessel invasion. Interpretation The integrated view of duct lesions and vascular remodeling suggests an active role, rather than a passive target, of lymphatic vessels in the metastasis of pancreatic cancer. Our 3-D image data provide insights into the pancreatic cancer microenvironment and establish the technical and morphological foundation for systematic detection and 3-D analysis of lymphatic vessel invasion. FUND: Taiwan Academia Sinica (AS-107-TP-L15 and AS-105-TP-B15), Ministry of Science and Technology (MOST 106-2321-B-001-048, 106-0210-01-15-02, 106-2321-B-002-034, and 106-2314-B-007-004-MY2), and Taiwan National Health Research Institutes (NHRI EX107-10524EI). |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|