The role played by a parathyroid hormone-like peptide (PLP) in the pathogenesis of hypercalcemia associated with malignancy has been examined. Elevated circulating levels of PLP were found more frequently in hypercalcemic cancer patients. A reduction of tumor burden in two of these patients resulted in concomitant decreases in both plasma calcium and plasma PLP. Immunoneutralization of endogenous PLP in a rat model of malignancy associated hypercalcemia resulted in a rapid and sustained reversal of the biochemical abnormalities manifest in the disease state. These studies, therefore, provided strong evidence for a role for PLP in the pathogenesis of hypercalcemia associated with neoplasia. The frequent association of squamous cell carcinoma with hypercalcemia and elevated circulating PLP levels prompted examination of a keratinocyte model of tumor progression for evidence of dysregulated PLP expression. Increased constitutive production of PLP, accompanied by resistance to previously identified regulatory agents, was demonstrated in the progression to the malignant phenotype. Finally, a potential autocrine or paracrine role for PLP in keratinocyte cell growth was suggested by the demonstration of functional adenylate cyclase-linked PLP receptors on an established keratinocyte cell line. These studies have therefore provided important insights into the role played by PLP as both an endocrine factor involved in the pathogenesis of malignancy associated hypercalcemia and as a potential autocrine/paracrine factor in keratinocyte homeostasis.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.70252 |
| Date | January 1992 |
| Creators | Henderson, Janet |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Division of Experimental Medicine.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001265681, proquestno: AAINN74465, Theses scanned by UMI/ProQuest. |
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