Solitary lung tumors and their spontaneous metastasis in athymic nude miceorthotopically implanted with human non-small cell lung cancer

We examined the tumorigenic and metastatic potentials of three human non-sm all cell lung cancer (NSCLC) cell lines, PC-14, A549 or Lu-99 cell lines su spended in Matrigel-containing phosphate-buffered saline were orthotopicall y implanted into the lungs of nude mice. The formation of a solitary tumor nodule in the lung was observed after the implantation of all cell lines. I ntrapulmonary implantation of PC-14 or Lu-99 cells resulted in spontaneous distant metastases. In contrast, A549 cells caused multiple intrapulmonary metastases to the right and left lobes of the lung without producing visibl e lymphatic metastasis. We also investigated the expression of matrix metal loproteinases (MMPs), urokinase-type plasminogen activator (U-PA), u-PA rec eptor (u-PAR) and c-MET in these cell lines in vitro and in vivo. Reverse t ranscription polymerase chain reaction (RT-PCR) analysis showed that the ex pression of MMP-2 and membrane-type 1 MMP (MT1-MMP) was elevated in PC-14 a s compared with the other two cell lines. In contrast, stronger expression of c-MET was observed in A549 than in PC-14 or Lu-99. These results indicat e that differential patterns of metastasis of lung cancer might be associat ed with differential expression of metastasis-associated molecules. Our ort hotopic implantation models display clinical features resembling those of N SCLC, and may provide a useful basis for lung cancer research.