The effect of heparin on the initial phase of metastasis formation

Circulating tumour cells in the blood, after endothelial attachment, will traverse the interstitial space and appear in the lymphatic system. Consequently the appearance of tumour cells in the thoracic duct lymph after injection into the blood stream may be correlated to the ability of the cells to stick to the endothelium and to traverse the interstitial space. The thoracic duct was cannulated in female SIV- 50 rats. 51 Cr-labelled Walker Carcinosarcoma 256 cells were injected via a polyethylene cannula from the femoral artery into the aorta beneath the diaphragm. Lymph specimens were sampled in intervals of 15 min over a period of 8 hr. Each lymph sample was passed through an 8 μ millipore filter. The presence of tumour cells was proved by morphological criteria after Papanicolaou staining and by scintillation counting of the filter. Normal animals show an initial slope of radioactivity beginning 15 min after tumour cell injection. Heparinization of the animals resulted in the loss of the initial tumour cells slope. Various viability tests showed that the heparin concentration used was not cytopathic. Since the clearance of tumour cells from the blood was not different in heparinized and non-heparinized rats, it is assumed that our results reflect a decreased interstitial transmigration of the tumour cells in the heparin group.