Establishment of patient-like SCID mouse model by orthotopically implanting primary cultured cells from surgically-resected lung cancer tissues.

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Background : Lymphogenous and hematogenous metastasis occurs frequently in patients with lung cancer. Suppression of these metastases provide an improvement in survival time in lung cancer patients. However, there is no patient-like animal model of these metastases of human lung cancer. We established a patient-like SCIIZ) mice model by orthotopic implantation using human non-small cell lung cancer (NSCLC) cell lines and first cultured lung cancer cells from resected tumor samples. Material and methods : Surgically-resected tissues of 5 patients with non-small cell lung cancer (NSCLC) were applied to a primary culture method using a collagen gel coated flask. We could maintain primary culture cells from 2 (FM205 and FT821cells) of 5 lung cancers, and made orthotopically implanted SOID mouse models. The size of both tumors in implanted sites of the lung increased with the time. Suspensions of 2.0x10^4 cancer cells with 10mg/ml Matrigel were injected into the left lung of SOID mice using … More a 30-gauge needle. We observed the progressive stages of development of lymphogenous and hematogenous metastasis from 2 week to 16 week in 4 lung cancer cell lines (Ma2, Ma10, Ma44-3, A549) and 2 primary culture cells(FM205 and FT821). And we evaluate a differences of RINA expression of 57 genes (anticancer drug-metabolism, -resistant enzyme, and DNA repair gene protein, etc) between implanted lung cancer tissues and lung cancer cell lines using DNA array. Results: All cell lines made tumor in the implanted site. The tumor in the implanted site of the lung became larger according to the time. Three cell lines (Ma44-3, FT821, and FM205) had the mediastinal lymph node metastasis. Ma10 cell line had no metastasis. A549 and Ma25 cell line bad both of mediastinal lymph node metastasis and intrapulmonary metastases. Ma2 cell line had solitary distant metastasis (adrenal gland, ovary, or lung). The degree of RNA expression of 57 genes in each implanted tumor correlated to that in the each cancer cell line (Pearson's correlation coefficient : r=0.8883-0.9533). Conclusion: The metastatic pattern of this model is very similar to that of clinical lung cancer, and the degree of expression of anticancer drug-related enzymes in the implanted tumor correlated to that of each cell line. We suppose that this model is useful for evaluating the inhibitory effect of anticancer drugs and the mechanism of lymphogenous and hematogenous metastasis. Less