Quantitative Studies of Autotransplantation of Human Cancer

Abstract

HIS STL~DY was prompted by the demon-T stration that cancer cells exfoliate into body fluids, including blood and lymph, in a very high percentage of patient~,l-~, 6-s, 14915 even those with early operable lesions.2, 4, 6 , 8 , 1 0 T h e high frequency of cancer cell contamination in casual specimens indicates that not all disseminated cancer cells develop into metastases and suggests that in many patients none produce metastatic lesions.This study was designed to test directly the autotransplantability of human cancer cells, on the assumption that subcutaneous autotransplantation would serve as a model of natural metastases, and to probe for possible explanations of the presumed failure of many disseminating cancer cells to implant and grow.Although the data are still preliminary, it is felt that they are significant and of sufficient interest to merit presentation at this time. MATERIALS AND METHODST h e patients were of 2 general categories:Chemotherapy Service patients with extensive recurrent or disseminated cancer for whom there remained no established method of treatment and who had tumor accessible to biopsy, and Gynecology Service patients who had had an exploratory or ablative operation but in whom the disease was not completely resectable or in whom the distribution of disease and type of operation was such that the probability of cure was extremely low. Most patients were interviewed before the procedure and inflormed of the experimental nature and general purpose of the study and the details of the procedure.

Cancer stem cells – old concepts, new insights

“…In the 1950s it was illustrated, by ethically controversial auto-transplantation experiments, that the development of a metastasis is a fairly inefficient process since only a small minority of all tumor cells is able to generate a distant recurrence. 84 Moreover, evidence is accumulating that numbers of circulating tumor cells in peripheral blood correlate with disease progression and prognosis. 85 However, the numbers of cells shed into the bloodstream, estimated to be as high as 10 6 cells per gram of cancer tissue daily, 86 is not reflected in the amount of distant metastasis found.…”

Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties

“…4,5 In vivo transplant assay, the injection of a small subset of cancer cells, also resulted in tumor development. 6,7 These results indicated the possibility that only a minor population possesses the ability to imitate tumors, whereas most lack tumor-initiating activities. These experimental observations have led to two general theories 8,9 : The stochastic model indicates that cancer is composed of a comparatively homogenous population and a few cells that undergo stochastic events and gain the potential to proliferate extensively and form new tumors.…”

A critique of the evidence for active host defence against cancer, based on personal studies of 27 murine tumours of spontaneous origin

“…The temptation is to assume that the recipient has " resisted " a large number of the malignant cells and that its " resistance " has been overwhelmed by the size of the inoculum. Indeed, an immunological interpretation has been suggested for the failure of large autografts of tumour cells in man (Southam and Brunschwig, 1961). However, the inability of an inoculum of tumour cells to establish itself as a progressively growing tumour does not necessarily imply any active exertion of the host against the tumour, and the use of the term " resis- , and by fibrin or brain extract (Peters and Hewitt, 1974); we have no reason to suspect that any of these additives would abrogate any specific immuine activity conceived to be directed against the viable tumour cells.…”