期刊
ONCOGENE
卷 27, 期 22, 页码 3145-3155出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.onc.1210973
关键词
lymph node; lymphangiogenesis; metastasis; p53; p19/Arf
资金
- NCI NIH HHS [R01-CA68328, R01-CA99517] Funding Source: Medline
The ability of tumor cells to metastasize is increasingly viewed as an interaction between the primary tumor and host tissues. Deletion of the p19/Arf or p53 tumor suppressor genes accelerates malignant progression and metastatic spread of 7,12-dimethylbenz(a) anthracene (DMBA)/12-O-tetradecanoyl-phorbol-13-acetate (TPA)induced squamous cell carcinomas, providinga model system to address mechanisms of metastasis. Here, we show that benign pre-metastatic papillomas from wildtype mice trigger lymphangiogenesis within draining lymph nodes, whereas there is no growth of primary tumor lymphatic vessels. Lymph node lymphangiogenesis is greatly accelerated in papilloma-bearing p19/Arf- or p53-deficient mice, which coincides with the greater propensity of these tumors to progress to carcinomas and to metastasize. The extent of accumulation of B cells within the tumor-draininglymph nodes of wild-type mice predicted the level of lymph node lymphangiogenesis and metastatic potential. Arf or p53 deficiency strongly accelerated lymph node immune cell accumulation, in a manner that was associated with the extent of lymph node lymphatic sinus growth. This immune cell accumulation and lymph node lymphangiogenesis phenotype identifies host anti-tumor responses that could drive metastatic spread of cancers via the lymphatics.
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