# MOLECULAR ULTRASTRUCTURE UNDERLYING CELL ADHESION

> **NIH NIH R01** · GEORGETOWN UNIVERSITY · 1988 · $181,594

## Abstract

Studies demonstrating the structural and functional specificities of
various cell-ECM attachment sites will be continued, with particular
emphasis on altered molecular mechanisms of cell adhesion, cell
de-adhesion, and invasion in transformed cells.  Our working hypotheses
are:  1) distinct, specific cell surface receptors are involved in
organizing cell attachments to fibronectin and collagen during dynamic
processes of cell adhesion and invasion, 2) ligands such as fibronectin can
help to regulate the distribution of their receptors and the cytoskeleton,
and 3) localized cell surface proteases are responsible for cell
contact-related dissolution of the ECM, which permits invasion.

Recent studies have demonstrated the existence of transformation-induced
cell surface proteases that degrade fibronectin and collagen at cell
contact sites.  Thus, the immediate goals of the present proposal are to
use monoclonal antibody probes to localize these transformation-sensitive,
invasion-associated proteases, to identify protease structural domains, and
to perturb molecular interactions involving proteases.  By this we plan to
determine the possible role of these proteases in transformed cell invasion
or as indicators of the metastatic potential of tumor cells.  The proposed
studies will also define possible collagen attachment sites at the electron
microscopic level, and determine whether such attachments function via
collagen receptors.  To do this, we will use in situ localization and
antibody inhibition approaches similar to those used for the
characterization of the fibronectin-receptor association.  Possible
regulatory roles of fibronectin and collagen in the organization of
attachment sites and in the invasion of the tumor cells will then be
studied by allowing these molecules to bind to the cell surface and
inhibiting their binding using specific monoclonal antibody probes and
synthetic peptides.

More specifically, we will seek to determine:  1) the molecular structure
and biochemical properties of cell surface proteases by the use of
hybridoma technology, 2) the roles of cell surface proteases in
transformation and invasion into fibronectin and collagen substrata, 3) the
expression and localization of cell surface receptors for collagen and
fibronectin at distinct attachment sites, 4) the regulatory roles of
fibronectin and collagen in the organization of adhesion sites in
transformed cells, and 5) the in vivo biological significance of cell
surface proteases or receptors in migration and invasion of tumor cells.

## Key facts

- **NIH application ID:** 3177847
- **Project number:** 5R01CA039077-05
- **Recipient organization:** GEORGETOWN UNIVERSITY
- **SAM.gov UEI:** TF2CMKY1HMX9
- **Principal Investigator:** WEN-TIEN CHEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $181,594
- **Award type:** 5
- **Project period:** 1984-07-01 → 1991-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3177847

## Citation

> US National Institutes of Health, RePORTER application 3177847, MOLECULAR ULTRASTRUCTURE UNDERLYING CELL ADHESION (5R01CA039077-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3177847. Licensed CC0.

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