# ALTERED PROTEOGLYCAN GENE EXPRESSION AND CANCER

> **NIH NIH R01** · THOMAS JEFFERSON UNIVERSITY · 1993 · $199,212

## Abstract

The overall goal of this application is to elucidate the mechanisms that
regulate the expression of proteoglycan genes in cancer, especially during
the formation of tumor stroma, a vital source of nutrients and growth-
supportive factors. The central hypothesis is that the structural,
compositional and molecular changes of proteoglycans in cancer stroma are
not random events, but rather are the result of specific interactions
between neoplastic and host mesenchymal cells. Proteoglycans are major
constituents of this tumor matrix and play pivotal roles not only in
matrix assembly, but also in the sorting, storing and delivering of growth
factors/cytokines. Aberrant expression of the two extracellular matrix
proteoglycans, decorin and versican, would contribute to tumor promotion
and invasion by providing a well-hydrated and growth factor-enriched
microenvironment.

The major goals for the next five years are to determine the molecular
organization of decorin and versican genes, to investigate the functional
activity of their respective promoters using recombinant DNA and gene
transfer techniques, and to generate transgenic animals overexpressing or
lacking these two important genes. The specific aims are to: (1) Determine
whether altered decorin and versican gene expression correlates with
invasive behavior of human colon cancer, (2) Determine the complete
genomic structure of decorin and versican genes, identify cis-acting DNA
regulatory elements in their promoters and test their functional
activities using heterologous gene constructs and transient transfection
assays, (3) Generate stable transfectants of human colon cancer cells
expressing high levels of decorin or versican proteoglycans, and
characterize tumorigenicity of the transfectants both in vitro and in
vivo, and (4) Develop transgenic mice overexpressing or lacking decorin
and versican genes.

These concerted research lines will provide information on the structural
and functional organization of decorin and versican genes and should
firmly establish their roles in tumorigenicity. The development of
transgenic animals with viral-induced overexpression or targeted
disruption of these two important genes should provide novel avenues of
research and possibly unravel unexpected functions for these two
proteoglycans. The results could lead to future approaches of cancer
prevention and treatment directed at hindering the expression of these two
proteoglycans thereby depriving the tumor cells of essential
macromolecules.

## Key facts

- **NIH application ID:** 3178501
- **Project number:** 2R01CA039481-09
- **Recipient organization:** THOMAS JEFFERSON UNIVERSITY
- **SAM.gov UEI:** R8JEVL4ULGB7
- **Principal Investigator:** RENATO V. IOZZO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $199,212
- **Award type:** 2
- **Project period:** 1988-09-01 → 1998-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3178501

## Citation

> US National Institutes of Health, RePORTER application 3178501, ALTERED PROTEOGLYCAN GENE EXPRESSION AND CANCER (2R01CA039481-09). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3178501. Licensed CC0.

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