Publication: The involvement of Helix pomatia lectin HPA binding N-acetylgalactosamine glycans in cancer progression
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Date
2000
Authors
Brooks, S.A.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
The lectin from Helix pomatia, the Roman
snail (HPA), recognises terminal alpha N-acetylgalactosamine
residues. A large number of lectin histochemical
studies have demonstrated that expression of
HPA-binding glycoproteins by cancer cells to be a
marker of metastatic competence and poor prognosis in a
range of common human adenocarcinomas, including
those of breast, stomach, ovary, oesophagus, colorectum,
thyroid and prostate. Around 80% of metastases arising
from primary breast cancer are predictably HPA
positive, but, intriguingly, around 20% do not express
HPA binding glycoproteins reflecting the complexity of
metastatic mechanisms and the further disruptions in
cellular glycosylation that attend tumour progression.
HPA binding is not an independent prognostic factor, but
is strongly associated with the presence of metastases in
local lymph nodes. It does appear to be independent of
other clinical features of prognostic importance such as
tumour size, histological grade, S-phase fraction, ploidy,
and there is little convincing evidence of any association
with oncogene expression or hormone receptor
positivity. The precise nature of the metastasisassociated
HPA binding partner(s) is a question of some
interest, but thus far remains unclear. HPA will
recognise, for example, the Tn epitope and blood group
A antigen, but its prognostic significance appears to be
through recognition of a much broader and heterogeneous
array of N-galactosaminylated glycoproteins.
Their synthesis appears to be mediated through
alteration in expression or activity of one or more of the
enzymes of glycosylation. The most likely putative roles
of HPA-binding ligands in the metastatic cascade may be
enhancement of invasive capacity, or interaction with an
as yet unidentified lectin-like receptor facilitating adhesion processes. The prognostic information
provided by HPA lectin histochemistry may be used
clinically to inform the physician and aid treatment
decisions; far more interesting is the challenge of further understanding the precise nature of the HPA-binding
ligands, and defining their role in the complex
mechanisms of metastasis.
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