Investigations into the potential role of aberrant N-acetylgalactosamine glycans in tumour cell interactions with basement membrane components.

The expression of the aberrant N-acetylgalactosamine (GalNAc) glycoconjugates, detected by binding of the lectin from Helix pomatia (HPA) is reported to be associated with metastatic competence and poor prognosis in a range of human adenocarcinomas, but the functional significance of the glycoconjugates in metastatic mechanisms is unknown. We have employed seven cell lines derived from normal breast epithelium, primary breast cancer and breast cancer metastases which stably express varying levels of HPA-binding glycoconjugates consistent with their derivation and phenotype. These cell lines have been thoroughly characterised and express identical profiles of HPA-binding glycoconjugates as tumour cells derived from clinical samples. Their ability to adhere to, and invade through, basement membrane components was investigated in a matrigel assay system, and the functional role of the aberrant GalNAc glycans assessed by competitive inhibition experiments using HPA. The behaviour of the cell lines in these assay systems was entirely consistent with their derivation and phenotype, but there was no evidence that the glycoconjugates of interest were functionally involved in adhesion or invasion mechanisms. Research in our laboratory is ongoing to seek a functional role for the HPA-binding glycoconjugates in other aspects of the metastatic cascade.