Parathyroid Hormone-related Protein in Normal and Neoplastic Canine Tissues: Immunohistochemical Localization and Biochemical Extraction

Abstract

Two polyclonal antibodies, directed against N-terminal amino acids (1-36) or the midregion (amino acids 34-53) of parathyroid hormone-related protein (PTHrP), were used to localize PTHrP in a variety of normal and neoplastic canine tissues. Parathyroid hormone (PTH) immunoreactivity was demonstrated using anti-bovine PTH (amino acids 14-34). The following tissues (among others) stained strongly positive for PTHrP: all layers of epidermal keratinocytes, with the most intense staining of the basal layer; hair follicle keratinocytes; myoepithelial cells of dermal apocrine glands, mammary glands, and apocrine glands of the anal sac; anal sac epithelium; mammary duct epithelium; and thyroid C cells. Adenocarcinomas of the anal sac stained moderately positive (5/22 dogs), weakly positive (11/22 dogs), or did not stain (6/22 dogs). Most parathyroid gland adenomas stained moderately (2/6 dogs) or weakly positive (3/6 dogs) for PTHrP. Squamous cell carcinomas (6/6 dogs) stained strongly positive. Lymphomas stained weakly positive (2/10 dogs) or did not stain (8/10 dogs). There was no consistent relationship between the staining intensity of the tumors and serum calcium concentrations of the dogs. The anti-PTH antibodies stained only parathyroid chief cells strongly positive. Concentrations of PTHrP were measured by radioimmunoassay in protein extracts from an adenocarcinoma derived from the apocrine glands of the anal sac, pancreas, kidney, liver, heart, thyroid, adrenal, and parathyroid glands. PTHrP concentrations varied from undetectable up to 150 pg/mg in normal tissues as compared with 2,000 pg/mg in apocrine adenocarcinoma of the anal sac.(ABSTRACT TRUNCATED AT 250 WORDS)

Establishment of a transplantable tumor line (IP) derived from rat pulmonary carcinoma, developing humoral hypercalcemia of malignancy in IP-bearing rats

“…von Kossa's stain, ×200 lial cells. [3,9,14,18], although the physiological functions in normal lung tissues have yet to be determined. In the present study, it was demonstrated by the immunohistochemistry, the RT-PCR method, and IRMA using culture supernatants that IP tumor cells produce PTHrP.…”

Skeletal metastasis of prostate adenocarcinoma in rats: Morphometric analysis and role of parathyroid hormone-related protein

“…Parathyroid hormone-related protein (PTHrP) was initially purified from human and animal tumors associated with the syndrome of humoral hypercalcemia of malignancy, and plays a central role in the pathogenesis of this paraneoplastic syndrome [15,16]. In addition, PTHrP has been suggested to promote skeletal metastasis of breast carcinomas [17][18][19][20][21][22].…”

Stromal and epithelial cells of the canine prostate express parathyroid hormone-related protein, but not the PTH/PTHrP receptor

“…Parathyroid hormone-related protein (PTHrP) was initially purified from human and animal tumors associated with the syndrome of humoral hypercalcemia of malignancy and plays a central role in the pathogenesis of this paraneoplastic syndrome [1,2]. Subsequently, PTHrP has been shown to be produced by many normal tissues, where it acts as a paracrine or autocrine cytokine with many potential functions, including regulation of cell growth and differentiation, regulation of smooth muscle cell relaxation, and transepithelial calcium transport [3].…”