Y. Waki et al., OSTEOPOROSIS-LIKE CHANGES IN WALKER CARCINOMA 256-BEARING RATS, NOT ACCOMPANIED WITH HYPERCALCEMIA OR PARATHYROID HORMONE-RELATED PROTEIN-PRODUCTION, Japanese journal of cancer research, 86(5), 1995, pp. 470-476
Walker carcinoma 256 (W256) was reported to induce hypercalcemia depen
dent on bone metastasis and/or parathyroid hormone-related protein (PT
HrP) in the rat, providing a model of the humoral hypercalcemia of mal
ignancy. In this study, after the subcutaneous inoculation of cells of
the W256/S line, which is maintained in this laboratory, into young f
emale Wister Imamichi rats (6 weeks old), serum calcium and phosphorus
levels changed only within the control range, whereas serum alkaline
phosphatase activity and urinary calcium level significantly increased
and urinary phosphorus decreased during the tumor growth, resulting i
n hypercalciuria and hypophosphaturia. W256/S did not express PTHrP-mR
NA, whereas LLC-W256 cells did express it. Serum PTHrP level was not c
hanged in W256/S-bearing rats. Osteoporosis-like changes, bone weight
loss, low contents of bone calcium and phosphorus, and a decrease in t
he bone mineral density (BMD), were observed in the femur 14 days afte
r the tumor inoculation. There was a pronounced decrease in the serum
17 beta-estradiol level during the tumor growth. The reduction of BMD
of femurs in W256/S-bearing rats was significantly inhibited by treatm
ent with salmon calcitonin or 17 beta-estradiol. On the basis of these
results, W256/S carcinoma-bearing rats seem to be a useful model for
osteoporosis of hypoovarianism.