Experimental analysis of factors affecting metastatic spread using naturally occurring tumours.

This paper describes the applications and latest results of recently developed techniques in metastasis research using naturally occurring animal and human tumours. Intravenous inoculation of cells from murine mammary tumours into syngeneic recipients has shown that some are consistently capable of heavy pulmonary colonisation (HCP) while others have low colonisation potential (LCP). These distinct characteristics are stable over wide cell-dose ranges. Autopsies on a sample of 100 consecutive tumour-bearing C3H/Avy mice revealed that the incidence of spontaneous metastasis is 26%. When inoculated intravenously, cells from some of the spontaneously metastatic primary tumours had HCP and others LCP. We now report that, knowing the degree of pulmonary colonisation of a particular tumour after intravenous inoculation, the degree of its spontaneous metastasis in the original host, and the dose-response relationships mentioned above, it is possible to back-titrate the degree of cell shedding from the tumour into the blood stream. Other experiments reported here demonstrate that separate mammary tumours on the same animal have independent colonisation potentials and growth rates, that tumours appearing later on an animal are not necessarily more capable of metastatic spread than the earlier ones, and that tumour weight and length of presence on the host do not show any strong correlation with spontaneous metastatic spread. A moderately significant association between pulmonary colonisation potential and tumour growth rate is reported and evidence corroborating our earlier observations that ability to colonise the lungs is possessed only by neoplastic mammary cells is also presented. Similar investigation are, of course, much more difficult to organise on tumour spread in man because of ethical and logistic considerations but it is possible to circumvent some of these difficulties and we refer to some of our ongoing studies.