p19/Arf and p53 suppress sentinel lymph node lymphangiogenesis and carcinoma metastasis.

Ruddell, A and Kelly-Spratt, K S and Furuya, M and Parghi, S S and Kemp, C J (2008) p19/Arf and p53 suppress sentinel lymph node lymphangiogenesis and carcinoma metastasis. Oncogene, 27 (22). pp. 3145-3155. ISSN 1476-5594

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Abstract

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, providing a model system to address mechanisms of metastasis. Here, we show that benign pre-metastatic papillomas from wild-type 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-draining lymph 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.

Item Type:	Article or Abstract
DOI:	10.1038/sj.onc.1210973
PubMed ID:	18059331
Keywords or MeSH Headings:	9,10-Dimethyl-1,2-benzanthracene; Animals; B-Lymphocytes/pathology; Carcinoma, Squamous Cell/blood supply/chemically induced/genetics/pathology; Cell Proliferation; Chemotaxis, Leukocyte/genetics; Cyclin-Dependent Kinase Inhibitor p16/genetics/physiology; Lymph Nodes/physiology; Lymphangiogenesis/genetics; Lymphatic Metastasis; Macrophages/pathology; Mice; Mice, Transgenic; Neovascularization, Pathologic/genetics; Skin Neoplasms/blood supply/chemically induced/genetics/pathology; Tetradecanoylphorbol Acetate; Tumor Suppressor Protein p53/genetics/physiology; Vascular Endothelial Growth Factor A/metabolism;
Subjects:	Diseases > Solid tumors Molecules > Proteins Cellular and Organismal Processes > Cell Physiology > Cell proliferation
Depositing User:	Library Staff
Date Deposited:	12 Mar 2010 23:46
Last Modified:	14 Feb 2012 14:43
URI:	http://authors.fhcrc.org/id/eprint/407

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