# MALIGNANCY ASSOCIATED HYPERCALCEMIA

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 1988 · $161,222

## Abstract

Hypercalcemia is a common and life-threatening complication of cancer.  In
patients with solid tumors, the occurance of hypercalcemia without skeletal
metastases suggests that a humoral mediator is responsible.  Considerable
evidence supports the proposal that this mediator is a tumor product that
mimics parathyroid hormone (PTH) by activating the same receptor, although
it is a distinct gene product.  Such proteins are characteristically
present in both conditioned culture medium and extracts of solid tumors
causing hypercalcemia.  Increases in the level of bioactive PTH in serum
and of nephrogenous cyclic AMP and phosphate in the urine of hypercalcemic
patients suggest that such PTH-like proteins have humoral effects.  We have
obtained evidence that after considerable purification, a PTH-like protein
from human renal carcinoma cells retains direct bone-resorbing effects.  We
propose to complete the purification of this protein, determine whether it
directly causes hypercalcemia, and develop a radioimmunoassay to detect it
in serum and tumor extracts.  Together, these results will critically test
the hypothesis that a PTH-like protein is the mediator of hypercalcemia
secreted by solid tumors.  The physiologic role of a PTH-like protein will
be clarified by studies of cultured keratinocytes, which have recently been
shown to secrete a protein that is indistinguishable from the tumor product.

In breast cancer, skeletal metastases characteristically precede the
development of hypercalcemia, indicating that accelerated bone resorption
has a local cause.  We hypothesize that a transforming growth factor
(TGF-Alpha) is a local mediator of the skeletal effects of breast
carcinoma; others have suggested it also has humoral effects when secreted
by other tumors.  We will use a panel of specific antagonists to determine
whether bone resorption produced by breast or other solid tumor cells is
mediated by TGF-Alpha.  These studies will provide a basis for the
understanding, and ultimately the treatment, of hypercalcemia in malignancy.

## Key facts

- **NIH application ID:** 3172528
- **Project number:** 5R01CA034738-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **SAM.gov UEI:** KMH5K9V7S518
- **Principal Investigator:** GORDON J STREWLER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $161,222
- **Award type:** 5
- **Project period:** 1986-08-15 → 1989-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3172528

## Citation

> US National Institutes of Health, RePORTER application 3172528, MALIGNANCY ASSOCIATED HYPERCALCEMIA (5R01CA034738-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3172528. Licensed CC0.

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