The mode of growth of experimental metastases in rabbit femora

Summary

Implantation of the Brown-Pierce carcinoma into a burr hole made within the cortex of rabbit femora has produced an experimental model which imitates the situation that occurs with spontaneous skeletal metastases in humans and animals. By killing the animals at regular intervals after tumour inoculation it has proved possible to follow the mode of growth of this tumour within bone. Initially the tumour grew amid the repair tissue associated with the cortical defect. When the tumour mass had reached a significant size osteoclastic resorption of cortical bone was seen to occur both within the vicinity and at some distance from the tumour. When the resorption cavities thus produced were expanded sufficiently the tumour grew into them both by direct extension and embolisation—small emboli were found in enlarged resorption cavities at sites remote from the main tumour mass. In the bones from fluorotic animals, because expanded resorption cavities existed before the onset of the experiment, this tumour invasion of cortical bone occurred earlier. Electron microscopy revealed large numbers of autophagic vacuoles and lysosomes within the tumour cells and it is suggested that lysosomal enzymes play an important role in bone resorption associated with tumours.