# STRUCTURE AND FUNCTION OF CELL SURFACE HYALURONATE

> **NIH NIH R01** · GEORGETOWN UNIVERSITY · 1993 · $177,553

## Abstract

The hyaluronate (HA) receptor is a glycoprotein of approximately Mr
85,000 which mediates the adhesion of cells to HA in the extracellular
matrix. It is present on a wide variety of cells including proliferating
epithelia, macrophages, lymphocytes and variety of tumor cells. Recently
this receptor has been shown to be closely related or identical to a
protein termed CD44 which mediates the homing of lymphocytes to mucosal
lymphoid tissue. Thus, the HA receptor/CD44 molecule is able to carry
out several distinct functions.

The central hypothesis of this application is that invasive tumor cells
express a form of CD44 which is capable of binding HA, and this in turn
allows these cells to invade through and degrade matrix containing HA.
Aspects of this hypothesis will be evaluated in the following specific
aims.

The first specific aim is to examine the structural requirements of CD44
binding to HA. Preliminary studies have shown that CD44 from the
invasive MDA-231 cell line binds HA, whereas that from the non-invasive
MCF-7 cell line does not. To determine the structural nature of this
difference, the CD44 from the two cell lines will be purified and
directly tested for their ability to bind HA. Also, the cell lines will
be compared by Northern Blotting and by the polymerase chain reaction to
determine if there are differences at the level of mRNA. And finally,
the CD44 will be tested for possible post-translational modifications
such as glycosylation and the presence of disulfide bonded material,
which might interfere with its ability to bind HA.

The second specific aim is to investigate the role of the HA
receptor/CD44 in the migration of tumor cells through a matrix rich in
HA. For this, an assay will be developed to measure the migration of
cells through cryostat sections of umbilical cord, a natural matrix
containing large amounts of HA. A panel of tumor cell lines will be
examined in this assay to determine if there is a correlation between
their invasive properties and their ability to bind [3H] HA. In
addition, the role of the receptor/CD44 in the invasive process will be
examined using specific antibodies and other blocking agents.

The final specific aim is to examine the role of the HA receptor/CD44 in
the degradation of HA by tumor cells. Preliminary studies demonstrated
that macrophages can degrade HA and this process is blocked by
monoclonal antibodies to the HA receptor. To determine if a similar
phenomenon occurs wit invasive tumor cells, a panel of tumor cells will
be examined for their ability to degrade [3H] HA, and correlated with
their invasive behavior. The relationship between invasion and
degradation of HA will be further tested using antibodies to the HA
receptor/CD44.

## Key facts

- **NIH application ID:** 3173189
- **Project number:** 5R01CA035592-08
- **Recipient organization:** GEORGETOWN UNIVERSITY
- **SAM.gov UEI:** TF2CMKY1HMX9
- **Principal Investigator:** CHARLES B UNDERHILL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $177,553
- **Award type:** 5
- **Project period:** 1984-07-01 → 1995-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3173189

## Citation

> US National Institutes of Health, RePORTER application 3173189, STRUCTURE AND FUNCTION OF CELL SURFACE HYALURONATE (5R01CA035592-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3173189. Licensed CC0.

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