Immunohistologic evaluation of parathyroid hormone-related protein in human lung cancer and normal tissue with newly developed monoclonal antibody

Abstract

With a newly developed monoclonal anti-PTHrP antibody, 4B3, the immunohistochemical localization of the parathyroid hormone-related protein (PTHrP) was studied on the formalin-fixed and paraffin-embedded sections of normal human tissues and various subtypes of lung cancer. Among normal epithelial tissues, keratinocytes in squamous epithelia, transitional and bronchial epithelia with squamous metaplasia, meningoepithelial cells, and mammary ductal cells with lactating changes showed positive immunoreactivity. Also, among endocrine tissues, cells in the parathyroid gland, pancreatic islets, adrenal cortex, pituitary gland, and testis were sporadically positive for PTHrP. These distribution patterns suggested that in a physiologic condition, PTHrP was closely related to keratinization and local secretion and/or the metabolism of calcium in specifically differentiated tissues. In lung cancer, however, PTHrP was detected in all cases of well-differentiated and moderately differentiated squamous cell carcinoma and in most cases of small cell carcinoma, irrespective of the patients' serum calcium level. However, PTHrP was not detected in two of five cases of poorly differentiated squamous cell carcinoma and in all cases of adenocarcinoma. Consequently, it was found that PTHrP was commonly produced by squamous cell carcinomas of the differentiated type, and that humoral hypercalcemia of malignancy could be induced when the PTHrP transgressed the homeostatic mechanisms.

Parathyroid hormone‐related peptide can regulate the growth of human lung cancer cells, and may form part of an autocrine TGF‐α loop

“…Human foetal lung is a plentiful source of PTHrP [S], as are many cases of carcinoma of the lung [4]. In contrast, nom?nl adult human lung does not appear to express the peptide.…”

“…Expression of PTHrP is not confined to tumour cells, having been isolated in a variety of normal human adult [4] and foetal tissues . The role it plays in adult physiology is unclear but in the case of the foetus it has been suggested that PTI-IrP may be responsible for the maintenance of the foetus-directed transplacental calcium gradient [S] and, additionally it may play a role as a foetal growth factor ['?I.…”

PTHrP drives breast tumor initiation, progression, and metastasis in mice and is a potential therapy target

“…PTHrP acts as an autocrine, paracrine, or intracrine factor in a wide range of developmental and physiological processes (7,8), it has growth-promoting and antiapoptotic properties (6), and it plays a crucial role in the development of the mammary gland and skeleton (8)(9)(10). Of special interest is the association of PTHrP with oncologic pathologies such as breast cancer (11,12) and lung (13)(14)(15), prostate (16)(17)(18), renal (19), colorectal (20)(21)(22), skin (23,24), and gastric carcinomas (25,26). Circulating levels of PTHrP generally correlate with the more advanced stages of cancer (20,(27)(28)(29)(30)(31)(32), and PTHrP regulates the expression of several tumor-relevant genes (33).…”

Cardiac Chondrosarcoma Producing Parathyroid Hormone-Related Protein

“…PTHrP has been isolated as a major factor responsible for HHM 12 and is known to be produced by various types of tumors. [13][14][15][16] Therefore, serological analysis of PTHrP might be useful in determining the cause of hypercalcemia in patients with malignant tumors. In the present case there was an extremely high preoperative serum concentration of C-PTHrP, which normalized immediately after the surgery, as did the elevated serum calcium concentration.…”