Deletion of p120-Catenin Results in a Tumor Microenvironment with Inflammation and Cancer that Establishes It as a Tumor Suppressor Gene

• DOI: 10.1016/j.ccr.2011.02.007
• Publication Date: 2011-04-13T11:41:57Z
• Authors: Douglas B. Stairs; Lauren J. Bayne; Ben Rhoades; Maria E. Vega; Todd J. Waldron; Jiri Kalabis; Andres Klein-Szanto; Ju-Seog Lee; Jonathan P. Katz; J. Alan Diehl; Albert B. Reynolds; Robert H. Vonderh...; Anil K. Rustgi
• Keywords: Inflammation; Cancer Research; Delta Catenin; 0303 health sciences; Esophageal Neoplasms; NF-kappa B; Catenins; Cell Differentiation; Cell Biology; Fibroblasts; Cadherins; 3. Good health; Mice; 03 medical and health sciences; Oncology; Cell Line, Tumor; Carcinoma, Squamous Cell; Animals; Humans; Genes, Tumor Suppressor; Mouth Neoplasms; Myeloid Cells; Cell Proliferation

p120-catenin (p120ctn) interacts with E-cadherin, but to our knowledge, no formal proof that p120ctn functions as a bona fide tumor suppressor gene has emerged to date. We report herein that p120ctn loss leads to tumor development in mice. We have generated a conditional knockout model of p120ctn whereby mice develop preneoplastic and neoplastic lesions in the oral cavity, esophagus, and squamous forestomach. Tumor-derived cells secrete granulocyte macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF), monocyte chemotactic protein-1 (MCP-1), and tumor necrosis factor-α (TNFα). The tumors contain significant desmoplasia and immune cell infiltration. Immature myeloid cells comprise a significant percentage of the immune cells present and likely participate in fostering a favorable tumor microenvironment, including the activation of fibroblasts.