Expression and in vitro modification of parathyroid hormone-related protein (PTHrP) and PTH/PTHrP-receptor in human myeloma cells

To elucidate the role of PTHrP in myeloma. we examined the expression level s of PTHrP and its receptor in human myeloma cell lines and clinical specim ens from 13 myeloma cases. In vitro modification of PTHrP expression and pr oduction induced by TGF-beta and PMA in PTHrP expressing myeloma cell lines was also investigated. PTHrP expression was detected in six our of seven m yeloma cell lines with an inverse correlation with the expression of its re ceptor, and in 10 out of 13 clinical specimens in varying degrees. The PTHr P expression and secretion into culture medium were enhanced by supplementa l TGF-beta and PMA. PMA also seemed to affect PTHrP upregulation via TCF-be ta activation. The fundamental role of PTHrP in bone lesions and hypercalce mia in myeloma may be important to consider even during the initial phase o f the disease and particularly in the progression of bone complications wit h hypercalcemia.