Lysosomal changes and enhanced metastatic growth: an experimental study of the effects of some non-ionic surfactants.

Abstract

AbstractThe effects on metastatic growth of Triton WR‐1339 and three chemically related non‐ionic detergents have been investigated in 40 hamsters bearing subcutaneous transplants of a metastasizing lymphoma (ML). Ten further untreated animals with tumour grafts and 20 normal animals without tumour grafts acted as controls. In hamsters without tumours, the four detergents commonly produced three hepatic changes: an increase in the liver/body weight ratio, an increase in stainable acid phosphatase, and an increase in the number and size of the lysosomes, together with ultrastructural changes. In tumour‐bearing animals, the detergents all produced a paradoxical effect, partially inhibiting growth of the tumour graft but markedly facilitating metastatic spread. More organs contained secondary tumours in the test groups, and the pattern of involvement in certain organs (liver, kidneys) was strikingly altered, with diffuse rather than focal metastatic growth. Detailed investigations of the liver established that treated animals all showed the same (but more profound) changes as those seen in detergent‐treated hamsters without tumours‐i.e., high liver/body weight ratios, high acid phosphatase scores, and lysosomal damage. No lysosomal lesions were found in untreated tumour‐bearing hamsters.In the discussion, it is stressed that the detergents tested acted principally on host (cf. tumour) tissues, and it is suggested that local lysosomal damage in lysosome‐rich organs such as the liver may be one factor whereby these detergents facilitate local tumour spread. Ways in which lysosomal lesions may affect local tumour growth are discussed, and analogies are drawn from previous work relating to lysosomal changes and the (associated) enhanced growth of mycobacteria. The implication of the present findings in relation to the old “soil” hypothesis of metastatic growth are indicated but the fallacies of premature generalizations about lysosomal changes and metastasis are stressed.