# ANALYSIS OF EXTRACELLULAR MATRIX OF TRANSFORMING CELLS

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 1993 · $193,213

## Abstract

The extracellular matrix (ECM) has such a significant influence on
normal growth and differentiation that is likely to play a role in
diseases involving abnormal growth and development, such as cancer.  The
long-term objective of this research is to define alterations in cell-
extracellular matrix interactions which play a role in the development
of this disease.  The ECM of cultured chicken embryo fibroblasts,
infected with temperature-sensitive (ts) mutants of Rous Sarcoma virus,
is modified during the early stages of transformation by the synthesis
and deposition of a small protein (Mr about 21,000).  Sufficient amounts
of the 21K protein have been purified to determine its function in the
matrix and potential role in transformation.  The protein promotes the
detachment of transforming cells from the ECM and stimulates
proliferation of quiescent cells.  Amino acid sequence data and other
properties indicate that the protein is related, but not identical, to
tissue inhibitor of metalloproteinases (TIMP/erythroid potentiating
activity (EPA).  We have detected five metalloproteinase inhibitor
activities (Mr about 20,000-26,000) in cultured chicken embryo
fibroblasts; these are designated ChIMPs (Chicken Inhibitor of
MetalloProteinases).  ChIMP-3 is the 21K protein.  This proposal is
designed to analyze the structure of ChIMP-3 using biochemical,
molecular and physical techniques and to test the hypothesis that the
protein promotes cell detachment from the ECM during oncogenic
transformation.  Electrophoresis, chromatography and mass spectrometry
will be used to define post-translational modifications.  Polyclonal
antibodies to ChIMP-3 will be used to aid in its characterization and to
describe its distribution in the matrix by immunofluorescence
microscopy.  The potential interaction of ChIMP-3 with other matrix
components will be established by electrophoresis, autoradiography and
binding studies.  The role of ChIMP-3 in expression of the transformed
phenotype will be investigated by inhibition studies with antisense
oligodeoxynucleotides.  Site-directed mutagenesis of ChIMP-3 will be
used to determine if the biological properties of this protein are
mediated through its metalloproteinase inhibitory activity.

## Key facts

- **NIH application ID:** 3179276
- **Project number:** 5R01CA039919-08
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **SAM.gov UEI:** KMH5K9V7S518
- **Principal Investigator:** SUSAN P HAWKES
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $193,213
- **Award type:** 5
- **Project period:** 1984-09-30 → 1996-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3179276

## Citation

> US National Institutes of Health, RePORTER application 3179276, ANALYSIS OF EXTRACELLULAR MATRIX OF TRANSFORMING CELLS (5R01CA039919-08). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3179276. Licensed CC0.

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