# EFFECTS OF PROSTATE CANCER ON SKELETAL TISSUE

> **NIH NIH R01** · MCGILL UNIVERSITY · 1991 · $79,314

## Abstract

Adenocarcinoma of the prostate exhibits a marked propensity to metastasize
to the skeleton where it comonly produces osteoblastic rather than
osteolytic lesions. Such lesions appear to be due to increased osteoblast
numbers and activity. We previously identified growth factors for cells of
the osteoblast phenotype in freshly isolated human prostatic cancer as well
as in benign prostatic hyperplasia. More recently we isolated a growth
factor for osteoblastlike cells from conditioned medium of a human prostate
cancer cell line (PC-3) which we identified as an amino-terminal fragment
(ATF) of urokinase-type plasminogen activator (uPA), a fragment containing
an "EGF-like" domain. We wish to test the hypothesis that overproduction
or persistence of ATFs containing this growth factor domain is important
in the pathogenesis of ostooblastic metastases by prostatic cancer. In our
initial series of studies we propose to compare the production of ATFs and
other uPA forms by prostatic cells and tissue and by other cancer cells and
tissues which are much less frequently associated with osteoblastic
metastases. Cell conditioned medium and tissue content will be examined by
sequence specific radioimmunoassays, Western blots and bioassays (mitogenic
and plasminogen activator). The mechanism for differences in cell or tissue
content which are observed will be explored by comparing uPA mRNA levels,
transcription rates, tissue-specific mRNA splicing and uPA metabolism. As
well, plasminogen activator inhibitor production will be compared. A second
series of studies will examine the spectrum of action, biopotency, and
mechanism of action of native, synthetic and recombinant ATFs on skeletal
tissue in vitro. Structure-function correlations will be made and cellular
specificity assessed. Effects on differentiated osteoblastic function and
on in vitro mineralization will be examined and characteristics of receptor
binding and of post-receptor mechanisms of action will be evaluated. The
studies therefore seek to determine whether discrete molecular domains of
uPA are involved in osseous growth versus osseous breakdown and could
provide a novel mechanism for the differential effects on skeletal
metabolism of cancer cells.

## Key facts

- **NIH application ID:** 3174815
- **Project number:** 2R01CA037126-07
- **Recipient organization:** MCGILL UNIVERSITY
- **SAM.gov UEI:** VJ62F6V2LE48
- **Principal Investigator:** DAVID GOLTZMAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $79,314
- **Award type:** 2
- **Project period:** 1984-09-30 → 1993-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3174815

## Citation

> US National Institutes of Health, RePORTER application 3174815, EFFECTS OF PROSTATE CANCER ON SKELETAL TISSUE (2R01CA037126-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3174815. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*