Lipoxygenase mediates invasion of intrametastatic lymphatic vessels and propagates lymph node metastasis of human mammary carcinoma xenografts in mouse
| Autor: | Satoshi Hirakawa, Katharina Krautgasser, Ingrid Raab, Felix Offner, Nicole Huttary, Brigitte Hantusch, Romana Kalt, Hitonari Nosaka, Katalin Nagy-Bojarszky, Susanne Wolbank, Klaus Kaserer, Michael Gnant, Katharina Viola, Sigurd Krieger, Helga Schachner, Sybille Madlener, Michael Detmar, Thomas Keller, Karin Lackner, Margaretha Rudas, Veronika Sexl, Martin Schreiber, Gregor Bartel, Thorsten J. Maier, Sandra Rezar, Georg Krupitza, Alexander Nader, Kari Alitalo, Agnes Davidovits, Sebastian M.B. Nijman, Dieter Steinhilber, Christine Schneckenleithner, Wolfgang Mikulits, Dontscho Kerjaschki, Zsuzsanna Bago-Horvath, Caroline Vonach, Monika Hämmerle, Helmut Dolznig |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Pathology
medicine.medical_specialty Axillary lymph nodes Lipoxygenase Sentinel lymph node Mammary Neoplasms Animal Biology Arachidonate 12-Lipoxygenase Metastasis Mice 03 medical and health sciences 0302 clinical medicine Multienzyme Complexes Recurrence Cell Line Tumor medicine Lymph node stromal cell Animals Arachidonate 15-Lipoxygenase Humans 12-Hydroxy-5 8 10 14-eicosatetraenoic Acid Neoplasm Metastasis Lymph sacs Lymph node 030304 developmental biology 0303 health sciences Carcinoma Carcinoma Ductal Breast General Medicine medicine.disease Coculture Techniques 3. Good health Treatment Outcome medicine.anatomical_structure Lymphatic system Lymphatic Metastasis 030220 oncology & carcinogenesis Female Lymph Neoplasm Transplantation |
| Zdroj: | Kerjaschki, D, Bago-Horvath, Z, Rudas, M, Sexl, V, Schneckenleithner, C, Wolbank, S, Bartel, G, Krieger, S, Kalt, R, Hantusch, B, Keller, T, Nagy-Bojarszky, K, Huttary, N, Raab, I, Lackner, K, Krautgasser, K, Schachner, H, Kaserer, K, Rezar, S, Madlener, S, Vonach, C, Davidovits, A, Nosaka, H, Hämmerle, M, Viola, K, Dolznig, H, Schreiber, M, Nader, A, Mikulits, W, Gnant, M, Hirakawa, S, Detmar, M, Alitalo, K, Nijman, S, Offner, F, Maier, T, Steinhilber, D & Krupitza, G 2011, ' Lipoxygenase mediates invasion of intrametastatic lymphatic vessels and propagates lymph node metastasis of human mammary carcinoma xenografts in mouse ', Journal of Clinical Investigation, vol. 121, no. 5, pp. 2000-12 . https://doi.org/10.1172/JCI44751 |
| ISSN: | 0021-9738 |
| Popis: | In individuals with mammary carcinoma, the most relevant prognostic predictor of distant organ metastasis and clinical outcome is the status of axillary lymph node metastasis. Metastases form initially in axillary sentinel lymph nodes and progress via connecting lymphatic vessels into postsentinel lymph nodes. However, the mechanisms of consecutive lymph node colonization are unknown. Through the analysis of human mammary carcinomas and their matching axillary lymph nodes, we show here that intrametastatic lymphatic vessels and bulk tumor cell invasion into these vessels highly correlate with formation of postsentinel metastasis. In an in vitro model of tumor bulk invasion, human mammary carcinoma cells caused circular defects in lymphatic endothelial monolayers. These circular defects were highly reminiscent of defects of the lymphovascular walls at sites of tumor invasion in vivo and were primarily generated by the tumor-derived arachidonic acid metabolite 12S-HETE following 15-lipoxygenase-1 (ALOX15) catalysis. Accordingly, pharmacological inhibition and shRNA knockdown of ALOX15 each repressed formation of circular defects in vitro. Importantly, ALOX15 knockdown antagonized formation of lymph node metastasis in xenografted tumors. Furthermore, expression of lipoxygenase in human sentinel lymph node metastases correlated inversely with metastasis-free survival. These results provide evidence that lipoxygenase serves as a mediator of tumor cell invasion into lymphatic vessels and formation of lymph node metastasis in ductal mammary carcinomas. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|