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Increased Growth Rate and Tumor Burden of Spontaneously Metastatic Walker 256 Cancer Cells in the Skeleton of Bisphosphonate-treated Rats¹

Department of Pathology and Oncology Research Group, McMaster University, Hamilton Regional Cancer Centre, Hamilton, Ontario, Canada L8V 5C2

We have studied the effect of 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (APD) on the morphology of rat bone and the metastatic behavior of Walker 256 (W256) cancer cells in the rat skeleton. Male Fischer rats (150–175 g) received s.c. injections for 7 days with APD (0.5 mg/kg body weight/day) (+ APD; n = 20) or with vehicle (-APD; n = 20). Subsequently, 10 + PD and 10 -APD rats received i.m. injections with W256 cells (+ W256), and the remaining rats received injections of vehicle (-W256). All rats were killed 14 days later. Trabecular bone volume was increased by 46 ± 3% by APD treatment alone and was decreased by 56 ± 7% (SEM) by W256 tumor burden alone. After 14 days of tumor burden, + APD/+ W256 rats had 3-fold more trabecular bone than did -APD/+ W256 rats. Despite this bone-sparing effect, APD treatment of + W256 rats was associated with a 2.6-fold increase in skeletal tumor burden, while metastatic tumor burden in the liver, lungs, and kidneys was unaffected. The increased skeletal tumor burden in + APD/+ W256 rats was accompanied by an increase in the growth rate of W256 cells located in bone. Independent of APD treatment, W256 cells located adjacent to trabecular bone surfaces had greater growth rates than did W256 cells in the marrow, located >50 µm from trabecular bone. In summary, the APD-induced increase in trabecular bone volume in rats is associated with a selective increase in skeletal tumor burden and an increased growth rate of W256 cells in the skeleton.

¹ Supported by Grant MA-10409 from the Medical Research Council of Canada.

² To whom requests for reprints should be addressed, at Hamilton Regional Cancer Centre, 699 Concession Street, Hamilton, Ontario, Canada, L8V 5C2.

Received 12/30/92. Accepted 9/ 9/93.

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