Vascular endothelial growth factor-D induces lymphangiogenesis and lymphatic metastasis in models of ductal pancreatic cancer.
The presence of lymphatic metastases is a strong indicator for poor prognosis in patients with ductal pancreatic cancer. In order to better understand the mechanisms controlling lymphatic growth and lymph node metastasis in human ductal pancreatic cancer, we analyzed the expression pattern of the va...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2005
|
| _version_ | 1826264790403645440 |
|---|---|
| author | Von Marschall, Z Scholz, A Stacker, SA Achen, MG Jackson, D Alves, F Schirner, M Haberey, M Thierauch, K Wiedenmann, B Rosewicz, S |
| author_facet | Von Marschall, Z Scholz, A Stacker, SA Achen, MG Jackson, D Alves, F Schirner, M Haberey, M Thierauch, K Wiedenmann, B Rosewicz, S |
| author_sort | Von Marschall, Z |
| collection | OXFORD |
| description | The presence of lymphatic metastases is a strong indicator for poor prognosis in patients with ductal pancreatic cancer. In order to better understand the mechanisms controlling lymphatic growth and lymph node metastasis in human ductal pancreatic cancer, we analyzed the expression pattern of the vascular endothelial growth factor-D (VEGF-D), its receptor VEGF-receptor-3 (VEGFR-3) and the lymphatic endothelium-specific hyaluronan receptor LYVE-1 in a panel of 19 primary human ductal pancreatic tumors and 10 normal pancreas specimens. We further addressed the biological function of VEGF-D for induction of lymphatic metastasis in a nude mouse xenograft model using two human ductal pancreatic cancer cell lines with overexpression of VEGF-D. Compared to normal human pancreas, pancreatic cancer tissue showed overexpression of VEGF-D and VEGFR-3 in conjunction with a high lymphatic vascularization as determined by immunohistochemistry and in situ hybridization. Tumors derived from VEGF-D-overexpressing cells had a higher microvessel density compared to their mock-controls, as determined based on CD31 immunohistochemistry. Importantly, these tumors also revealed a significant induction of intra- and peritumoral lymphatics, as judged from immunohistochemical detection of LYVE-1 expression. This was associated with a significant increase in lymphatic vessel invasion by tumor cells and an increased rate of lymphatic metastases, as indicated by pan-cytokeratin reactive cells in lymph nodes. Our results suggest that VEGF-D plays a pivotal role in stimulating lymphangiogenesis and lymphatic metastasis in human ductal pancreatic cancer, and therefore represents a novel therapeutic target for this devastating disease. |
| first_indexed | 2024-03-06T20:13:30Z |
| format | Journal article |
| id | oxford-uuid:2b60c9f7-af32-43a4-ae26-ff5efb944cda |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:13:30Z |
| publishDate | 2005 |
| record_format | dspace |
| spelling | oxford-uuid:2b60c9f7-af32-43a4-ae26-ff5efb944cda2022-03-26T12:30:32ZVascular endothelial growth factor-D induces lymphangiogenesis and lymphatic metastasis in models of ductal pancreatic cancer.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:2b60c9f7-af32-43a4-ae26-ff5efb944cdaEnglishSymplectic Elements at Oxford2005Von Marschall, ZScholz, AStacker, SAAchen, MGJackson, DAlves, FSchirner, MHaberey, MThierauch, KWiedenmann, BRosewicz, SThe presence of lymphatic metastases is a strong indicator for poor prognosis in patients with ductal pancreatic cancer. In order to better understand the mechanisms controlling lymphatic growth and lymph node metastasis in human ductal pancreatic cancer, we analyzed the expression pattern of the vascular endothelial growth factor-D (VEGF-D), its receptor VEGF-receptor-3 (VEGFR-3) and the lymphatic endothelium-specific hyaluronan receptor LYVE-1 in a panel of 19 primary human ductal pancreatic tumors and 10 normal pancreas specimens. We further addressed the biological function of VEGF-D for induction of lymphatic metastasis in a nude mouse xenograft model using two human ductal pancreatic cancer cell lines with overexpression of VEGF-D. Compared to normal human pancreas, pancreatic cancer tissue showed overexpression of VEGF-D and VEGFR-3 in conjunction with a high lymphatic vascularization as determined by immunohistochemistry and in situ hybridization. Tumors derived from VEGF-D-overexpressing cells had a higher microvessel density compared to their mock-controls, as determined based on CD31 immunohistochemistry. Importantly, these tumors also revealed a significant induction of intra- and peritumoral lymphatics, as judged from immunohistochemical detection of LYVE-1 expression. This was associated with a significant increase in lymphatic vessel invasion by tumor cells and an increased rate of lymphatic metastases, as indicated by pan-cytokeratin reactive cells in lymph nodes. Our results suggest that VEGF-D plays a pivotal role in stimulating lymphangiogenesis and lymphatic metastasis in human ductal pancreatic cancer, and therefore represents a novel therapeutic target for this devastating disease. |
| spellingShingle | Von Marschall, Z Scholz, A Stacker, SA Achen, MG Jackson, D Alves, F Schirner, M Haberey, M Thierauch, K Wiedenmann, B Rosewicz, S Vascular endothelial growth factor-D induces lymphangiogenesis and lymphatic metastasis in models of ductal pancreatic cancer. |
| title | Vascular endothelial growth factor-D induces lymphangiogenesis and lymphatic metastasis in models of ductal pancreatic cancer. |
| title_full | Vascular endothelial growth factor-D induces lymphangiogenesis and lymphatic metastasis in models of ductal pancreatic cancer. |
| title_fullStr | Vascular endothelial growth factor-D induces lymphangiogenesis and lymphatic metastasis in models of ductal pancreatic cancer. |
| title_full_unstemmed | Vascular endothelial growth factor-D induces lymphangiogenesis and lymphatic metastasis in models of ductal pancreatic cancer. |
| title_short | Vascular endothelial growth factor-D induces lymphangiogenesis and lymphatic metastasis in models of ductal pancreatic cancer. |
| title_sort | vascular endothelial growth factor d induces lymphangiogenesis and lymphatic metastasis in models of ductal pancreatic cancer |
| work_keys_str_mv | AT vonmarschallz vascularendothelialgrowthfactordinduceslymphangiogenesisandlymphaticmetastasisinmodelsofductalpancreaticcancer AT scholza vascularendothelialgrowthfactordinduceslymphangiogenesisandlymphaticmetastasisinmodelsofductalpancreaticcancer AT stackersa vascularendothelialgrowthfactordinduceslymphangiogenesisandlymphaticmetastasisinmodelsofductalpancreaticcancer AT achenmg vascularendothelialgrowthfactordinduceslymphangiogenesisandlymphaticmetastasisinmodelsofductalpancreaticcancer AT jacksond vascularendothelialgrowthfactordinduceslymphangiogenesisandlymphaticmetastasisinmodelsofductalpancreaticcancer AT alvesf vascularendothelialgrowthfactordinduceslymphangiogenesisandlymphaticmetastasisinmodelsofductalpancreaticcancer AT schirnerm vascularendothelialgrowthfactordinduceslymphangiogenesisandlymphaticmetastasisinmodelsofductalpancreaticcancer AT habereym vascularendothelialgrowthfactordinduceslymphangiogenesisandlymphaticmetastasisinmodelsofductalpancreaticcancer AT thierauchk vascularendothelialgrowthfactordinduceslymphangiogenesisandlymphaticmetastasisinmodelsofductalpancreaticcancer AT wiedenmannb vascularendothelialgrowthfactordinduceslymphangiogenesisandlymphaticmetastasisinmodelsofductalpancreaticcancer AT rosewiczs vascularendothelialgrowthfactordinduceslymphangiogenesisandlymphaticmetastasisinmodelsofductalpancreaticcancer |