E-Cadherin Loss Accelerates Tumor Progression and Metastasis in a Mouse Model of Lung Adenocarcinoma.

Autor:	Sinkevicius KW; 1 Stem Cell Program, Division of Hematology/Oncology and Pulmonary and Respiratory Diseases, Children's Hospital Boston, Boston Massachusetts.; 2 Department of Genetics, Harvard Medical School, Boston, Massachusetts.; 3 Harvard Stem Cell Institute, Cambridge, Massachusetts; and., Bellaria KJ; 1 Stem Cell Program, Division of Hematology/Oncology and Pulmonary and Respiratory Diseases, Children's Hospital Boston, Boston Massachusetts.; 2 Department of Genetics, Harvard Medical School, Boston, Massachusetts.; 3 Harvard Stem Cell Institute, Cambridge, Massachusetts; and., Barrios J; 1 Stem Cell Program, Division of Hematology/Oncology and Pulmonary and Respiratory Diseases, Children's Hospital Boston, Boston Massachusetts.; 2 Department of Genetics, Harvard Medical School, Boston, Massachusetts.; 3 Harvard Stem Cell Institute, Cambridge, Massachusetts; and., Pessina P; 1 Stem Cell Program, Division of Hematology/Oncology and Pulmonary and Respiratory Diseases, Children's Hospital Boston, Boston Massachusetts.; 2 Department of Genetics, Harvard Medical School, Boston, Massachusetts.; 3 Harvard Stem Cell Institute, Cambridge, Massachusetts; and., Gupta M; 1 Stem Cell Program, Division of Hematology/Oncology and Pulmonary and Respiratory Diseases, Children's Hospital Boston, Boston Massachusetts.; 2 Department of Genetics, Harvard Medical School, Boston, Massachusetts.; 3 Harvard Stem Cell Institute, Cambridge, Massachusetts; and., Brainson CF; 1 Stem Cell Program, Division of Hematology/Oncology and Pulmonary and Respiratory Diseases, Children's Hospital Boston, Boston Massachusetts.; 2 Department of Genetics, Harvard Medical School, Boston, Massachusetts.; 3 Harvard Stem Cell Institute, Cambridge, Massachusetts; and., Bronson RT; 4 Dana-Farber/Harvard Cancer Center, Harvard Medical School, Boston, Massachusetts., Kim CF; 1 Stem Cell Program, Division of Hematology/Oncology and Pulmonary and Respiratory Diseases, Children's Hospital Boston, Boston Massachusetts.; 2 Department of Genetics, Harvard Medical School, Boston, Massachusetts.; 3 Harvard Stem Cell Institute, Cambridge, Massachusetts; and.
Jazyk:	angličtina
Zdroj:	American journal of respiratory cell and molecular biology [Am J Respir Cell Mol Biol] 2018 Aug; Vol. 59 (2), pp. 237-245.
DOI:	10.1165/rcmb.2017-0210OC
Abstrakt:	Metastatic disease is the primary cause of death of patients with lung cancer, but the mouse models of lung adenocarcinoma do not accurately recapitulate the tumor microenvironment or metastatic disease observed in patients. In this study, we conditionally deleted E-cadherin in an autochthonous lung adenocarcinoma mouse model driven by activated oncogenic Kras and p53 loss. Loss of E-cadherin significantly accelerated lung adenocarcinoma progression and decreased survival of the mice. Kras;p53;E-cadherin mice had a 41% lung tumor burden, invasive grade 4 tumors, and a desmoplastic stroma just 8 weeks after tumor initiation. One hundred percent of the mice developed local metastases to the lymph nodes or chest wall, and 38% developed distant metastases to the liver or kidney. Lung adenocarcinoma cancer cell lines derived from these tumors also had high migratory rates. These studies demonstrate that the Kras;p53;E-cadherin mouse model better emulates the tumor microenvironment and metastases observed in patients with lung adenocarcinoma than previous models and may therefore be useful for studying metastasis and testing new lung cancer treatments in vivo.
Databáze:	MEDLINE
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