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Hypercalcemia in cancer.

T J Martin1, V Grill

  • 1Department of Medicine, University of Melbourne, St Vincent's Hospital, Fitzroy, Vic., Australia.

The Journal of Steroid Biochemistry and Molecular Biology
|September 1, 1992
PubMed
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Humoral hypercalcemia of malignancy (HHM) is often caused by parathyroid hormone-related protein (PTHrP). This newly identified hormone is linked to calcium disturbances in various cancers and has potential roles in fetal development and adult organs.

Area of Science:

  • Endocrinology
  • Oncology
  • Biochemistry

Background:

  • Hypercalcemia is a known complication of hematological malignancies and solid tumors, with or without bone metastases.
  • Humoral hypercalcemia of malignancy (HHM) presents features similar to primary hyperparathyroidism.
  • The underlying mechanisms of HHM, particularly in the absence of bone metastases, require further elucidation.

Purpose of the Study:

  • To identify and characterize the specific factor responsible for humoral hypercalcemia of malignancy (HHM).
  • To investigate the role of a novel hormone in calcium regulation associated with cancer.
  • To explore the tissue distribution and potential functions of this newly discovered hormone.

Main Methods:

  • Identification, isolation, and cloning of a novel protein.

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  • Sequence homology analysis comparing the novel protein with parathyroid hormone (PTH).
  • Immunohistochemical tissue localization studies in both cancerous and normal tissues.

    • Main Results:

    • A parathyroid hormone-related protein (PTHrP) was identified as the likely mediator of calcium disturbances in HHM.
    • PTHrP shares limited amino-terminal sequence homology with PTH but originates from a separate gene.
    • PTHrP was localized in various cancers (squamous cell, renal cortical, breast, adult T-cell leukemia/lymphoma) and normal tissues (keratinocytes, placenta, fetal parathyroid glands).

    Conclusions:

    • PTHrP is the primary cause of humoral hypercalcemia of malignancy (HHM).
    • PTHrP is a distinct hormone with a significant role in cancer-associated hypercalcemia.
    • PTHrP likely possesses important endocrine functions in fetal development and paracrine roles in adult tissues.