5-6-dichloro-1-beta-d-ribofuranosylbenzimidazole-3--5--monophosphorothioate and Carcinoma-256--Walker

The rat Walker 256 carcinoma is an animal model for humoral hypercalcemia of malignancy. This tumor produces and secretes parathyroid hormone (PTH)-related protein (PTHrP), a likely mediator for this syndrome. In this study, we investigated the effect of PTHrP on Walker 256 tumor cell proliferation. We found that [Tyr36]human (h)PTHrP (1-36)NH2 and hPTHrP (1-86), unlike hPTHrP (38-64)NH2, stimulate DNA synthesis dose-dependently in these cells. A similar mitogenic effect was also observed with bovine (b)PTH (1-34) or (Nle8.18, Tyr34)bPTH (3-34)NH2. Moreover, addition of anti-hPTHrP (1-34) neutralizing antibodies decreased tumor cell growth. Conversely, 10(-4)M dibutyryl cAMP or Sp-cDBIMPS (a cAMP analogue) inhibited DNA synthesis in these cells, being incompetent at lower doses. PTHrP or PTH failed to stimulate cAMP production, but they induced a cytosolic calcium transient increase in these cells. These findings support an autocrine role of PTHrP in the regulation of this tumor growth.

Topics: 1-Methyl-3-isobutylxanthine; Adenylyl Cyclases; Animals; Antibodies; Bucladesine; Calcium; Carcinoma 256, Walker; Cattle; Cell Division; Cytosol; Dantrolene; Dichlororibofuranosylbenzimidazole; DNA, Neoplasm; Female; Flow Cytometry; Humans; Hypercalcemia; Parathyroid Hormone; Parathyroid Hormone-Related Protein; Peptide Fragments; Proteins; Rats; Rats, Wistar; Teriparatide; Thionucleotides; Thymidine; Tumor Cells, Cultured