Demonstration of the stem cell nature of clonogenic tumor cells from lung cancer patients.

The tumor cell colony-forming efficiency in soft agarose was evaluated in 190 specimens obtained from patients with either small cell carcinoma of the lung (SCCL) or adenocarcinoma of the lung (ACL). Tumor cell colony formation was observed in 45 out of 53 (84%) specimens containing cytopathologically identifiable SCCL tumor cells obtained from a variety of metastatic sites. Tumor cell colony formation was also observed in 6 out of 10 specimens containing ACL tumor cells. The colony-forming efficiency for these lung cancer specimens ranged from 0.003 to 0.72% per nucleated cell plated and from 0.05 to 1.5% per tumor cell plated. There were no differences in plating efficiency for SCCL and ACL. The tumor cell origin of the cells in the agarose colonies was confirmed by cytologic examination, flow cytometric DNA content analysis, and electron microscopy examination. The 'stem cell' nature was demonstrated by the ability of colonies to form typical SCCL or ACL tumors when inoculated into athymic nude mice. In addition, continuous tumor cell lines were established from several specimens forming tumors in nude mice. These data confirm the tumor cell origin and 'stem cell' nature of lung cancer cell colonies growing in soft agarose. Whether the low colony-forming efficiency represents a property inherent in the tumor cells, or a defect in the culture system, remains to be determined.