Metastasis-enhancing effect of heparin and its relationship to a lipoprotein factor

The effect of low-dose heparin on spontaneous metastasis formation was studied with the PA-III rat prostate adenocarcinoma cell line model system. In LW rats given heparin iv at a dose of 1,000 U/kg body weight (three times/wk), the metastatic spread of implanted PA-III cells from the footpad through ipsilateral lymphatics to the lungs was enhanced. The weights of the draining lymph nodes (popliteal, inguinal, and axillary) and the number of lung tumor colonies were significantly increased compared with those in the saline-treated control tumor-bearing rats. The growth of the primary tumor was also enhanced. Heparin alone did not induce enlarged lymph nodes in rats nor did it change the growth pattern of PA-III cells in vitro. The accelerated metastatic spread of the PA-III cells was possibly related to the destruction of the oncolytic activity of the very low-density lipoprotein by the lipoprotein lipases induced by the iv administration of heparin. However, the possibility that other mechanisms could be operative in this phenomenon has not been ruled out.