# MOLECULAR ULTRASTRUCTURE UNDERLYING CELL ADHESION

> **NIH NIH R01** · GEORGETOWN UNIVERSITY · 1992 · $218,632

## Abstract

The metastatic potential of tumor cells is the most important determinant
for the prognosis of neoplastic disease.  Among the molecular steps
required for successful metastasis are several discrete events that
involve the invasion of tumor cells through connective tissue barriers.
Cell invasiveness concerns adhesion to and proteolysis of extracellular
matrices and basement membranes, as well as cell motility.  This proposal
focuses on plasma membrane-associated proteases and adhesion molecules
of human malignant melanoma cells that are important in mediating the
invasiveness and metastatic potential of these cells.  Recent work from
this laboratory identifies several novel membrane proteases from human
malignant melanoma cells, chicken embryonic cells, chicken transformed
cells, and chicken embryos.  Unique cell surface structures called
invadopodia are present on cells expressing the malignant phenotype and
have been shown to be involved in the invasiveness of cells.  The
invadopodia are sites of active tyrosine-phosphorylation, localization
of beta1 integrins, and active degradation of the extracellular matrix
by membrane proteases.  The goals of this proposal are (1) to determine
the biochemical nature of membrane proteases by the combined approaches
of protease activity assays, cellular localization by monoclonal antibody
production, sub-cellular fractionation, inhibitor- and antibody-affinity
chromatography, protein biochemistry including microsequencing, and
molecular cloning, (2) to determine how membrane proteases interact with
other proteases to activate degradation, and their role in the expression
of cell invasiveness, (3) to investigate the control mechanisms of cell
invasion, particularly focusing on the direct or indirect interaction of
membrane proteases with putative motility factors including the laminin
A chain peptide, autocrine motility factor, acidic fibroblast growth
factor, and interleukin-I during the induction of invadopodia and with
the human integrins that localize to invadopodia during the stabilization
of invasion-associated membranes, and (4) to determine the expression and
localization of protease and adhesion molecules in experimental invasion
and metastasis models and human tumors by scanning confocal microscopy
and immuno-electron microscopy.

## Key facts

- **NIH application ID:** 3177844
- **Project number:** 2R01CA039077-09
- **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:** 1992
- **Award amount:** $218,632
- **Award type:** 2
- **Project period:** 1984-07-01 → 1996-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3177844

## Citation

> US National Institutes of Health, RePORTER application 3177844, MOLECULAR ULTRASTRUCTURE UNDERLYING CELL ADHESION (2R01CA039077-09). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3177844. Licensed CC0.

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