This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fukumoto, S. Articles by Ogata, E. Search for Related Content PubMed PubMed Citation Articles by Fukumoto, S. Articles by Ogata, E.

Secretion of Parathyroid Hormone-like Activity from Human T-Cell Lymphotropic Virus Type I-infected Lymphocytes¹

Fourth Department of Internal Medicine, University of Tokyo School of Medicine, Bonkyo-ku, Tokyo [S. F., T. M., T. W., E. O.]; Department of Pharmacology, Teikoku Hormone Manufacturing Company, Kawasaki, Kanagawa [H. T.]; and Department of Medicine, Kochi Medical School, Kochi, Kochi [I.M.], Japan

Because many patients with adult T-cell leukemia/lymphoma (ATLL) develop hypercalcemia with similar characteristics to those of humoral hypercalcemia of malignancy (HHM) (Arch. Intern. Med., 148: 921–925, 1988), we investigated if ATLL cells produce parathyroid hormone (PTH)-like activity. Conditioned media from cultures of human T-cell lymphotropic virus type I-infected cell line (MT-2) as well as peripheral lymphocytes from a hypercalcemic ATLL patient stimulated cyclic AMP production in osteoblast-like rat osteogenic sarcoma cells (UMR 106) and bone resportion in organ cultures of fetal mouse calvaria. Furthermore, the stimulation of cyclic AMP production by conditioned medium of MT-2 cells was inhibited by human PTH(3–34), indicating that MT-2 cells secrete PTH-like activity. The PTH-like activity from MT-2 cells was chromatographically indistinguishable from the one extracted from a solid tumor causing HHM. The present results along with our previous observation that MT-2 cells constitutively express mRNA for PTH-related protein (Biochem. Biophys. Res. Commun., 154: 1182–1188, 1988) demonstrate that a PTH-like activity is synthesized and secreted by these cells, and are consistent with the hypothesis that elaboration of PTH-like activity by ATLL cells may be the mechanism by which hypercalcemia develops in ATLL patients as well as in solid cancer patients with HHM. However, these results do not rule out the possibility that other factors such as interleukin 1 are also involved and may act in concert with PTH-like activity in the development of hypercalcemia in ATLL.

¹ The present study was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan, and grants from Arima Memorial Foundation and from the Research Foundation for Bone Metabolism sponsored by Chugai Pharmaceutical Co.

² To whom requests for reprints should be addressed, at Fourth Department of Internal Medicine, University of Tokyo School of Medicine, 3-28-6 Mejirodai, Bunkyo-ku, Tokyo 112, Japan.

Received 11/ 4/88. Revised 3/13/89. Accepted 4/19/89.

This article has been cited by other articles:

				C. Parrula, B. Zimmerman, P. Nadella, S. Shu, T. Rosol, S. Fernandez, M. Lairmore, and S. Niewiesk Expression of Tumor Invasion Factors Determines Systemic Engraftment and Induction of Humoral Hypercalcemia in a Mouse Model of Adult T-cell Leukemia Vet. Pathol., September 1, 2009; 46(5): 1003 - 1014. [Abstract] [Full Text] [PDF]

				V. Richard, M. D. Lairmore, P. L. Green, G. Feuer, R. S. Erbe, B. Albrecht, C. D'Souza, E. T. Keller, J. Dai, and T. J. Rosol Humoral Hypercalcemia of Malignancy : Severe Combined Immunodeficient/Beige Mouse Model of Adult T-Cell Lymphoma Independent of Human T-Cell Lymphotropic Virus Type-1 Tax Expression Am. J. Pathol., June 1, 2001; 158(6): 2219 - 2228. [Abstract] [Full Text] [PDF]

				Y. Nishigaki, Y. Ohsaki, E. Toyoshima, and K. Kikuchi Increased Serum and Urinary Levels of a Parathyroid Hormone-related Protein COOH Terminus in Non-Small Cell Lung Cancer Patients Clin. Cancer Res., June 1, 1999; 5(6): 1473 - 1481. [Abstract] [Full Text] [PDF]

				A. Takaori-Kondo, K. Imada, I. Yamamoto, A. Kunitomi, Y. Numata, H. Sawada, and T. Uchiyama Parathyroid Hormone-Related Protein-Induced Hypercalcemia in SCID Mice Engrafted With Adult T-Cell Leukemia Cells Blood, June 15, 1998; 91(12): 4747 - 4751. [Abstract] [Full Text] [PDF]