A group from University of Oulu, Faculty of Biochemistry and Molecular Medicine, Oulu, Finland, etc. has reported that expression level of α-GalNAc recognized by Helix Pomatia agglutinin (HPA) lectin correlated significantly with invasive potential of cancer cells.
Authors investigated glycosylation profiles of the nine cancer cell lines with different invasiveness by using lectin microarray glycan profiling.
Out of 43 lectins in the lectin microarray, only five lectins (HPA, PTL-1, AJA, MAL I, PWM) were found to correlate either positively or negatively with the invasive potential of the cancer cells. Multiple linear regression analyses further demonstrated that these five lectins accounted for 97% of the variation observed in the cancer cell invasive phenotype, HPA alone accounted for 58% of the variation, and together with PTL-1, HPA accounted for 76% of the variation, while the rest (AJA, MAL I, PWM) correlated negatively and accounted for 7% each. Thus, increased expression of HPA-binding glycotopes (O-linked α-GalNAc) in cancer cells appears to be the main factor promoting cancer cell invasive phenotype.
Then, HPA-binding proteins were pulled down with HPA lectin, and identified with LC-MS/MS.
Of these, glycoproteins (EGFR, MMP-14, β4-, β1-, α2- and αV integrin) in HPA pulldown samples were markedly enriched in highly invasive cells relative to poorly invasive cells, indicating that these proteins carry increased levels of a terminal α-GalNAc in their glycans. Of these same glycoproteins, the EGFR and α2 integrin correlated significantly with cancer invasive potential.