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Parathyroid Hormone-Related Protein-Induced Hypercalcemia in SCID
Mice Engrafted With Adult T-Cell Leukemia Cells
Akifumi Takaori-Kondo,
Kazunori Imada,
Itsuo Yamamoto,
Akane Kunitomi,
Yasuharu Numata,
Hitoshi Sawada, and
Takashi Uchiyama
From the Institute for Virus Research, Kyoto University, Sakyo-ku,
Kyoto, Japan; the Department of Radiology, Shiga University of Medical
Sciences, Otsu, Shiga, Japan; and the Department of Internal Medicine,
Kokura Memorial Hospital, Kokurakita-ku, Kita-kyusyu, Japan.
Parathyroid hormone-related protein (PTHrP) is considered to be one
of the main causes of hypercalcemia associated with adult T-cell
leukemia (ATL). To clarify the role of PTHrP and bone remodeling in the
development of hypercalcemia in ATL, we examined the SCID mouse model
of ATL that has previously been shown to mimic the disease in humans.
Using this model, we found clear elevations in serum levels of calcium
and C-terminal PTHrP (C-PTHrP). PTHrP mRNA was highly expressed in ATL
cells proliferating in vivo. After the development of hypercalcemia,
ATL mice were killed and bone histomorphometric analysis was performed.
Bone volume was clearly decreased in the ATL mice. In comparison to
control SCID mice, bone formation indices were very low in the ATL
mice. Surprisingly, no significant difference was detected between the
ATL mice and the control SCID mice in eroded surface/bone surface
(ES/BS), a parameter of bone resorption. To our knowledge, the model
presented here is the first animal model of ATL with humoral
hypercalcemia. This is in contrast to previously reported,
well-characterized animal models of human solid tumors associated with
humoral hypercalcemia of malignancy (HHM). Furthermore, this model not
only provides us with the opportunity to study the mechanisms
underlying development of elevated calcium levels in ATL, but also
allows us to test new therapeutic agents designed to treat
hypercalcemia.
Blood, Vol. 91 No. 12 (June 15), 1998:
pp. 4747-4751
© 1998 by The American Society of Hematology.
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