Quantitation of tumorigenic disseminating and arrested cancer cells

The numbers of potentially tumorigenic cancer cells released into the circulation and secondarily arrested in the lungs of mice bearing B16F10 melanomas or Lewis lung carcinomas were systematically quantified throughout i.m. tumour growth using a bioassay procedure capable of detecting as few as 10 to 100 tumorigenic cells in the circulation or lungs. Viable disseminating cancer cells were detectable within 4 days of i.m. tumour growth and reached 10(6) per 0.5 ml of blood in carcinoma-bearers and 2 X 10(4) per 0.5 ml in melanoma-bearers; 98% of mice with circulating cancer cells had potentially tumorigenic cells in their lungs, even in the absence of overt metastases. The numbers of cancer cells present in the circulation and lungs were related to the growth rate of the i.m. lesion, more cells being released from faster-growing tumours. The numbers of tumorigenic carcinoma cells were compared with the total numbers of cells released into the circulation as quantitated by direct counting procedures, and it was found that the vast majority of these circulating cells were potentially tumorigenic. These studies provide quantitative information about cancer cell input into the metastatic process. Also, the bioassay procedure provides a useful experimental model for the development of regimens for therapy of metastases since it is a sensitive method of monitoring not only the size of disseminated populations of cancer cells but also their clinically relevant property namely, their tumorigenic potential.