Passive immunization with anti-parathyroid hormone-related protein monoclonal antibody markedly prolongs survival time of hypercalcemic nude mice bearing transplanted human PTHrP-producing tumors

Parathyroid hormone (PTH)-related protein has been shown to be a factor responsible for hypercalcemia of malignancy. Recent studies have shown the presence of mRNA for PTH-related protein in lactating breast tissue, suggesting a physiological role for this peptide during lactation. In the present study, we evaluated the effect of neutralization of PTH-related protein activity in lactating mice (by passive immunization) on various parameters of maternal and neonatal calcium homeostasis. PTH-related protein bioactivity, as tested in the adenylate cyclase assay, was present in mouse milk, and this activity was completely neutralized by the antisera used in the present study. In lactating mice, the effects of injection of PTH-related protein antisera on maternal serum calcium concentrations, milk calcium and phosphorus concentration, pup growth, dam femur calcium content, and pup calcium content were similar to those of the injection of normal rabbit serum. Therefore, maternal PTH-related protein does not appear to have a role in calcium homeostasis during lactation.

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Effects of Humoral Hypercalcemia of Malignancy on the Parathyroid Gland in Nude Mice

Veterinary Pathology ◽

10.1177/030098589202900409 ◽

1992 ◽

Vol 29 (4) ◽

pp. 343-350 ◽

Cited By ~ 8

Author(s):

A. Gröne ◽

T. J. Rosol ◽

W. Baumgärtner ◽

C. C. Capen

Keyword(s):

Parathyroid Hormone ◽

Nude Mice ◽

Secretory Granules ◽

Related Protein ◽

Male Mice ◽

Chief Cells ◽

Cytoplasmic Area ◽

Parathyroid Hormone Related Protein ◽

Low Calcium Diet ◽

Low Calcium

The ultrastructure of parathyroid chief cells was examined from four groups of nude mice (NIH: Swiss) with different serum calcium concentrations. The groups consisted of eight male mice with hypercalcemia induced by transplantable canine adenocarcinoma (CAC-8), eight female mice with hypercalcemia induced by infusion of parathyroid hormone-related protein, ten male control mice, and six male mice fed a low calcium (0.01%) diet. Hypercalcemia induced by malignancy or parathyroid hormone-related protein infusion was associated with low serum phosphorus concentration, a decrease in the number of secretory and prosecretory granules in the parathyroid chief cells, and an increase in the cytoplasmic area of chief cells. Prominent myelinlike membranous whorls were present in the cytoplasm of chief cells of tumor-bearing and parathyroid hormone-related protein-infused hypercalcemic mice. Mice fed a low calcium diet had decreases in the number of secretory granules and cell area but increases in the number of prosecretory granules compared with control mice. The number of mitochondria and the nuclear area of chief cells were similar in all four groups. The prominent membranous whorls and increased cytoplasmic area of chief cells from these hypercalcemic mice mark these cells as distinctly different from the parathyroid chief cells of other species with hypercalcemia.

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