# EPIGENETIC REGULATION OF THE SWARM RAT

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 1987 · $98,078

## Abstract

The toxic side effects of chemotherapy and debilitation caused by
radical surgery have prompted the search for homeostatic
alternatives to conventional cancer therapeutic modalities.  In
view of the many similarities between embryonic development
and neoplasia, one area of promise in this search is the possibility
that the malignant behavior of cells can be regulated by
epigenetic mechanisms as are the cells of the embryo.  More
specifically, when competent malignant cells are placed in an
appropriate microenvironment or individuation field they may
pursue a normal developmental course and become benign.  This
proposal outlines the rationale and methods to explore this
possibility by using the morphogenetic properties of demineralized
diaphyseal bone matrix to effect the growth and differentiation of
neoplastic cells.  We have previously shown that the Swarm rat
chondrosarcoma is induced by the microenvironment of bone
morphogenesis to undergo a series of phenotypic changes which
resemble terminal chondrocyte differentiation.  We will
determine the mechanisms through which this occurs by
examining intracellular and extracellular markers of chondrocytic
differentiation.  The former include ultrastructure, clacium
binding sites and enzyme histochemistry.  The latter utilizes
monoclonal antibodies against extracellular matrix components to
examine qualitative and/or quantitative changes.  A number of
other sarcomas and continuous cell lines will also be evaluated for
their ability to respond to morphogenetic induction.  The specific
aspects to be evaluated include in vivo modulation of tumor
growth, tumor stem cell pluripotentiality, histogenetic
specificity, developmental vs. nonspecific growth regulation and
mesenchymal competence.  In addition, we will continue to
develop an in vitro model in an attempt to elucidate the specific
molecular natures of the inductors operative in the bone
matrix/tumor cell interaction.  In so doing, we hope to provide
both fundamental insight into the mechanisms of naturally
occurring neoplasms and a clinically applicable method for the
treatment of mesenchymal cancer.

## Key facts

- **NIH application ID:** 3173100
- **Project number:** 2R01CA035533-04A1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **SAM.gov UEI:** MW8JHK6ZYEX8
- **Principal Investigator:** Gary J. Miller
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $98,078
- **Award type:** 2
- **Project period:** 1984-03-01 → 1990-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3173100

## Citation

> US National Institutes of Health, RePORTER application 3173100, EPIGENETIC REGULATION OF THE SWARM RAT (2R01CA035533-04A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3173100. Licensed CC0.

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