Biomedical Engineering Reference
In-Depth Information
3.2 Hyaluronic Acid in Tumour Targeting and Delivery
3.2.1 CD44 Receptor Interactions
HA, also called hyaluronan, is a naturally occurring polysaccharide
and the only non-sulfated glycosaminoglycan that is abundant in
the extracellular matrix and synovial fluids of all vertebrates. HA
is a highly negatively-charged polymer composed of alternating
disaccharide units of
d
-glucuronic acid and
N
-acetyl-
d
-glucosamine
with β (1-4) interglycosidic linkage [1]. HA is known to establish
multivalent interactions with other extracellular macromolecules that
determine the extracellular matrix (ECM) porosity and permeability.
It was known that the tumour cells easily migrate within the ECM,
which is rich in hyaluronan. These HA rich matrices are also known
to create hydrated pathways that facilitate the penetration of tumour
cells. Thus the tumour types that overproduce HA are most likely
to enhance the tumour progression. It is well documented that
HA plays several important organisational roles in tissue integrity,
angiogenesis, wound healing and cell motility through interaction
with receptors on the cell membrane [2]. CD44 and RHAMM have
been identified as HA receptors and are known to be overexpressed
in many types of cancer cell, demonstrating enhanced binding and
internalisation of HA [3]. The RHAMM receptor is also a HA
binding protein but has a totally different structure from that of
CD44 and the hyaluronan binding sites contain a motif of a minimal
site of interaction with hyaluronan. CD44 on the other hand is the
best characterised transmembrane HA receptor and, because of its
wide distribution, it is considered to be the major receptor on most
cell types. Blocking the interaction of HA with CD44 receptors was
previously demonstrated to inhibit the majority of the HA-CD44
mediated cellular functions.
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