# CELL INTERACTIONS--EXPRESSION OF PRENEOPLASTIC MARKERS

> **NIH NIH R01** · LOCKHEED MARTIN ENERGY SYSTEMS, INC. · 1993 · $229,094

## Abstract

Transforming growth factor type-beta (TGF-beta) is a member of a large
family of polypeptides which play an important role in the regulation of
normal cell growth and differentiation.  Alterations in the ability to
respond to TGF-beta may be involved in the loss of growth control
associated with tumor development.

We have observed that differentiated tracheal epithelial cells sloughed
into the culture medium can activate latent TGF-beta.  The ability to
activate TGF-beta was not observed in cultured preneoplastic or
neoplastic tracheal cells.   Given the importance of the activation step
in regulation of cellular responses to TGF-beta the following questions
will be addressed: (a) Do differentiated cells within the intact tissue
have the capacity to activate latent TGF-beta? (b) Do differentiated
cells harvested from tumorigenic populations grown in vivo or in culture
exhibit the capacity to activate TGF-beta? (c) Do differentiated cells
from other tissues likewise exhibit the capacity to activate TGF-beta
either in culture or within the intact tissue? (d) What factor associated
with differentiated tracheal cells activates latent TGF-beta?

At present much of the information concerning the cellular response to
TGF-beta has been obtained with cultured cells.  In the proposed
experiments the relevance of these observations to the intact tissue will
be evaluated.  In particular, the following will be investigated:(a) What
cell population in the intact tissue binds TGF-beta? (b) What cell
population within the intact tissue responds to TGF-beta? (c) Does
communication between contacting cells affect the cellular response to
TGF-beta? (d) Does the effect of TGF-beta on nonepithelial stromal cells
indirectly affect the response of epithelial cells within the same
tissue? (e) Does cell shape affect the binding and/or response to TGF-
beta in culture?

The proposed experiments are designed to test the following working
hypothesis.  Latent TGF-beta is produced by basal cells. Latent TGF-beta
is then activated by differentiated cells within the tissue.  Activated
TGF-beta in turn regulates proliferation of stem cells.  During
neoplastic progression there is a break at some point(s) in this negative
feedback loop.

## Key facts

- **NIH application ID:** 3172472
- **Project number:** 5R01CA034695-11
- **Recipient organization:** LOCKHEED MARTIN ENERGY SYSTEMS, INC.
- **Principal Investigator:** MARGARET TERZAGHI-HOWE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $229,094
- **Award type:** 5
- **Project period:** 1983-05-01 → 1996-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3172472

## Citation

> US National Institutes of Health, RePORTER application 3172472, CELL INTERACTIONS--EXPRESSION OF PRENEOPLASTIC MARKERS (5R01CA034695-11). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3172472. Licensed CC0.

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