# NEOPLASTIC MODULATION OF PROTEOGLYCAN METABOLISM

> **NIH NIH R01** · THOMAS JEFFERSON UNIVERSITY · 1989 · $124,372

## Abstract

The active interplay between malignant and host mesenchymal cells
leads to the formation of a tumor stroma which provides the
infrastructures the tumor cells require for successful growth and
infiltration.  The central hypothesis of this research plan is that
the formation of this matrix is a specialized process under the
direct control of neoplastic cells and that changes in proteoglycan
composition may ultimately affect neoplastic cell behavior.  This
hypothesis derives, in part, from our previous in vivo observations
that chondroitin sulfate proteoglycan (CS-PG) is markedly increased
in tissue extracts of human colon carcinoma and that the connective
tissue stroma is the primary site of synthesis and accumulation of
this gene product.  Our subsequent studies have shown that colon
carcinoma cells can modulate the biosynthesis of proteoglycans in
human colon fibroblasts and smooth muscle cells by inducing the
production of a CS-PG similar to that found in tissue extracts of
colon carcinoma.

The present research proposal is designed to explore further this
complex phenomenon of tumor matrix production and to define some
of the mechanisms that regulate its expression.  The specific aims
are to:

1. Define the biochemical, structural and immunological
characteristics of the protein core(s) of the proteoglycans
synthesized by human colon smooth muscle cells and fibroblasts,
and investigate changes induced by colon carcinoma cells.

2.  Determine whether the stimulation of CS-PG is associated with
increased levels of PG core specific mRNA, and whether these
changes in mRNA levels reflect changes in transcription rates
and/or RNA stability both in cultured cells and in colon carcinoma
tissue.

3. Interfere with the process of excessive CS-PG production by
depleting the intracellular pools of PG protein core or hexosamine,
and determine key rate limiting factors of the transport, secretion
and turnover of these gene products.

The research should provide insights into the mechanisms by which
rumor cells modulate PG metabolism in host mesenchymal cells.
Potentially leading to future approaches of cancer prevention and
treatment directed at hindering the formation of tumor stroma,
thereby depriving the tumor cells of their essential support
services.

## Key facts

- **NIH application ID:** 3178504
- **Project number:** 5R01CA039481-05
- **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:** 1989
- **Award amount:** $124,372
- **Award type:** 5
- **Project period:** 1988-09-01 → 1993-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3178504

## Citation

> US National Institutes of Health, RePORTER application 3178504, NEOPLASTIC MODULATION OF PROTEOGLYCAN METABOLISM (5R01CA039481-05). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3178504. Licensed CC0.

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