Development of a sensitive two-site immunoradiometric assay for parathyroid hormone-related peptide: evidence for elevated levels in plasma from patients with adult T-cell leukemia/lymphoma and B-cell lymphoma.

Abstract

We have developed a sensitive immunoradiometric assay for PTH-related peptide (PTHrP) using a monoclonal antibody against PTHrP(1-34) and a polyclonal antibody against PTHrP(50-83), with recombinant human PTHrP(1-87) as the standard. The detection limit of the immunoradiometric assay was 0.5 pmol/L, and plasma PTHrP(1-87) concentrations in 110 healthy subjects were 0.8 +/- 0.01 pmol/L, with the upper limit of the normal range being 1.1 pmol/L. Increased circulating PTHrP(1-87) concentrations were demonstrated in all 46 cancer patients with hypercalcemia, but not in patients with primary hyperparathyroidism, chronic renal failure, or hypoparathyroidism. Normalization of serum calcium levels after resection of tumors was shown to correlate well with that of plasma PTHrP(1-87) concentrations in 2 cancer patients. High circulating PTHrP(1-87) levels were also demonstrated in 12 out of 13 hypercalcemic patients with adult T-cell leukemia/lymphoma and in 7 out of 8 hypercalcemic patients with non-Hodgkin's lymphoma especially of B-cell type. These results suggest that PTHrP is a major humoral factor responsible for the hypercalcemia frequently associated with adult T-cell leukemia/lymphoma and also with B-cell lymphoma.

Mechanisms and treatment of hypercalcemia of malignancy

“…Hypercalcemia ensues only when PTHrP reaches a threshold concentration that replaces and surpasses the analogous actions of PTH. Hypercalcemia attributed to elevated concentrations of humoral PTHrP has been estimated to occur in 33-84% of breast cancers [33][34][35][36][37][38], 46-76% of lung cancers [35,36,38], 21-63% of non-Hodgkin's lymphomas (NHLs) [38][39][40] and 92% of adult T-cell leukemia/ lymphomas due to the human T-lymphotropic virus type 1 (HTLV-1) infection [39]. Infrequently, PTHrPmediated hypercalcemia occurs in head and neck tumors [41,42], renal cell carcinoma [43,44], bladder cancer [45], pancreatic carcinoma [46], hepatocellular carcinoma [47], carcinoid tumors [48] and melanoma [49].…”

Cancer and Bone*

“…This topic will be discussed in a later section. Using a sensitive two-site immunoradiometric assay, other investigators have noted increased plasma PTHrP concentrations in patients with adult T cell leukemia and B cell lymphoma (198). PTHrP in hypercalcemia associated with hematological malignancies.…”

Human T-cell lymphotropic-I-associated leukemia/lymphoma

“…Recently, the mechanism for the hypercalcemia in ATL has been elucidated in detail [51][52][53][54][55][56][57][58][59][60][61]. ATL cells secrete an excessive amount of parathyroid hormonerelated peptide (PTHRP) in patients with hypercalcemia [53][54][55][56].…”

“…ATL cells secrete an excessive amount of parathyroid hormonerelated peptide (PTHRP) in patients with hypercalcemia [53][54][55][56]. Ikeda et al [52,57] investigated the molecular mechanism and found that the protein kinase C and protein kinase A pathways are vital in inducing transcription of the PTHRP gene in HTLV-I-infected T cells.…”