# CANCER-HYPERCALCEMIA: NEW SECRETED BONE-RESORBING FACTOR

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 1988 · $152,330

## Abstract

Hypercalcemia in malignancy appears to result most commonly from
accelerated bone resorption induced by soluble factors secreted by tumor
cells.  The identity of these factors and their mechanism(s) of action,
however, are largely unknown.  We have identified a potent bone-resorbing
factor in medium of cultured tumor cells from a patient with
transitional-cell carcinoma ("TCC") of the bladder, hypercalcemia and no
bone metastases.  These cells are tumorigenic and cause hypercalcemia when
implanted in athymic nude mice.  A bone-resorbing factor identical to that
in TCC-cell culture medium was found in the patient's urine and in extracts
of tumors grown in nude mice.  This factor, a peptide of approximately
13,000 daltons, survives denaturation (8M urea), reduction (65mM DTT) and
heating (56 C) and causes bone resorption by a mechanism dependent upon
stimulation of bone prostaglandin synthesis.  This factor is different from
others recently described as it does not stimulate adenylate cyclase and
lacks biologic and chemical features of transforming growth factors.  The
major goals of this proposal are to purify this factor in quantities
sufficient to determine its structure, to develop specific antibodies
directed against it, and to further test its biologic actions in vivo and
in vitro.  We will purify this factor to homogeneity from conditioned
medium of TCC cell cultures on the basis of its bone-resorbing activity in
a sensitive in vitro bioassay.  Structure of the purified peptide will be
determined using standard chemical techniques, complemented by
microsequence analysis of labeled factor prepared by biosynthetic
incorporation of radioactive amino acids.  Monoclonal antibodies to the
factor will be prepared by in vitro or in vivo immunization of mice and
used to develop immunoaffinity reagents for factor purification and
radioassays for its measurement.  Sufficient purified factor will be
obtained to permit direct study of its biologic actions in vivo and in
vitro and, thereby, to enable us to test the hypothesis that this
tumor-derived bone-resorbing factor is the cause of the hypercalcemia
induced by this tumor in vivo.  These studies may have profound
implications for understanding normal bone development and remodeling as
well as the pathophysiology of the humoral hypercalcemia of malignancy.

## Key facts

- **NIH application ID:** 3171248
- **Project number:** 5R01CA033320-06
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **SAM.gov UEI:** FLJ7DQKLL226
- **Principal Investigator:** GINO V SEGRE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $152,330
- **Award type:** 5
- **Project period:** 1983-06-01 → 1990-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3171248

## Citation

> US National Institutes of Health, RePORTER application 3171248, CANCER-HYPERCALCEMIA: NEW SECRETED BONE-RESORBING FACTOR (5R01CA033320-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3171248. Licensed CC0.

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