title: Orthotopically implanted SCID mouse model of human lung cancer suitable for investigating metastatic potential and anticancer drug effects.
abstract: To evaluate the effects of drugs in clinical settings, an animal model of lung cancer similar to clinical cancer is necessary. Our previous studies described an SCID mouse model using orthotopic implantation of the human lung cancer cell line which mimicked the lymph node metastasis of patients with lung cancer. In this study, we made animal models that reflected various metastatic forms of lung cancer in humans. We applied our procedure to 6 lung cancer cell lines. Suspensions of 2.0 x 10(4) cancer cells were injected into the left lung of SCID mice. We evaluated the mRNA expressions of 52 proteins related to the metabolism of and resistance to anticancer drugs of each tumor cell line and its orthotopically implanted tumor using a customized cDNA array. Three lung cancer cell lines had the potential of lymphogenous metastasis and 3 cell lines had the potential of hematogenous metastasis in this model system. The A549 line showed multiple metastases, and Ma2 line showed solitary metastasis. The expression of 52 genes in each implanted tumor was closely correlated with that in each cell lines (correlation coefficients: 0.8883-0.9533), and the gradient of the regression line was more than 0.9. This model was similar to the metastatic form in patients with lung cancer. The similar expression of proteins in each tumor cell line in vitro and implanted tumor in vivo gives an advantage in evaluating the effects of molecular-targeted drugs and the relationship between specific genes and tumor potential in preclinical studies.
authors.affiliation: Department of Oncological and Regenerative Surgery, Institute of Health Biosciences, University of Tokushima Graduate School, 3-chome, Kuramoto-cho, Tokushima City 770-8503, Japan. kondo@clin.med.tokushima-u.ac.jp
authors.forename: Kazuya
authors.initials: K
authors.lastname: Kondo
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Fujino
authors.forename: Takanori
authors.initials: T
authors.lastname: Miyoshi
authors.forename: Hisashi
authors.initials: H
authors.lastname: Ishikura
authors.forename: Shoji
authors.initials: S
authors.lastname: Sakiyama
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Monden
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary*; D008207:Lymphatic Metastasis; D051379:Mice; D016513:Mice, SCID; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy*; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D016588:Anticarcinogenic Agents; D009363:Neoplasm Proteins; D012333:RNA, Messenger