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Adenylate cyclase-stimulating, bone-resorbing and B TGF-like activities in canine apocrine cell adenocarcinoma of the anal sac

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Summary

Canine apocrine cell adenocarcinoma of the anal sac (APO-AS) is a spontaneously occurring tumor that causes humorally medicated hypercalcemia in 90% of cases. To further define the nature of the responsible mediator in APO-AS, we examined tumor extracts from five APO-AS and four control tumors for adenylate cyclase-stimulating activity (ACSA). All extracts from APO-AS contained potent ACSA, whereas the four control tumors did not. The ACSA extracted from one tumor demonstrated a dose response curve parallel to that of synthetic bovinePTH-(1–34) and was 80% inhibited by Nle8,18,Tyr34 bPTH-(3–34)amide at a concentration of 10−5 M. Extracts from three APO-AS and three control tumors were also examined forin vitro bone-resorbing activity (BRA). All APO-AS contained significant BRA, stimulating resorption 1.47 to 2.13-fold over basal, whereas none of the control tumors stimulated resorption. Purification of one extract using C18 reverse-phase high pressure liquid chromatography (RP-HPLC) resulted in a single sharp peak of ACSA which was 400-fold purified compared with the initial extract. This pool also contained significant bone-resorbing activity, whereas none of the adjacent pools did. Purification of a second extract using sequential CN and C18 RP-HPLC followed by size exclusion HPLC resulted in material that was at least 10,000-fold purified, and showed co-purification of ACSA and B TGF-like activity.

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Authors and Affiliations

  1. St. Francis Hospital and Medical Center, Hartford, Connecticut, USA

    Michael Centrella

  2. The Animal Medical Center, New York, New York, USA

    Robert E. Matus & Margorie L. Brooks

  3. The West Haven Veterans Administration Medical Center, West Haven, Connecticut, USA

    Terence Wu & Karl L. Insogna

  4. Section of Comparative Medicine, Yale University School of Medicine, 333 Cedar Street, P.O. Box 3333, 06510, New Haven, CT, USA

    Eleanor C. Weir

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  1. Eleanor C. Weir
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  2. Michael Centrella
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  4. Margorie L. Brooks
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  5. Terence Wu
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  6. Karl L. Insogna
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Weir, E.C., Centrella, M., Matus, R.E. et al. Adenylate cyclase-stimulating, bone-resorbing and B TGF-like activities in canine apocrine cell adenocarcinoma of the anal sac. Calcif Tissue Int 43, 359–365 (1988). https://doi.org/10.1007/BF02553279

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  • DOI: https://doi.org/10.1007/BF02553279

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