Expression of TriSia & PolySia in Human Cancers

Introduction: The a2,8-linked polySia chains that post-translationally modify NCAM is an anti-adhesive glycotope that plays a critical role in modulating cell-cell adhesive and cell migration interactions during embryonic development, neural plasticity and tumor metastasis. When re-expressed on the surface of several human tumors it can facilitate their detachment and metastasis to different sites. The a2,8 triSia structure was recently shown by C. Sato and colleagues for the first time to reside on four glycoproteins expressed in a developmental stage-dependent manner in mouse brain (Glycobiology, 2010). The exact function of the triSia glycoproteins is unknown, but has been implicated in oligodendrocyte differentiation, similar to the function of the triSia structure on gangliosides. Objective: To determine the level of a2,8-tri-Sia and polySia expression in human carcinomas. Experimental Method: Western blot analyses with antibodies specific for recognizing either triSia or polySia. Results: (1) Expression of the triSia and polySia glycotopes on human carcinomas are independent of each other; (2) Of the total of 192 breast, lung, stomach and colon cancers analyzed, 72% were polySia positive and 64% were triSia positive; (3) PolySia was differentially expressed at higher rates in lung tumors/lymph nodes compared with triSia (93% vs 63%), while triSia was differentially expressed in 81% of the colon cancers vs. 66% for polySia; (4) Both glycotopes were expressed at high rates in stomach CA (87.5% for polySia) and 93.7% for triSia); (5) Expression of both triSia and polySia were found principally on glycoprotein with Mr ∼160, 140 & 110. Conclusions: (1) An unexpectedly high percentages of human cancers were found to express both the triSia and polySia glycotopes, suggesting that these glycoproteins may be potentially novel diagnostic and prognostic biomarkers for cancer screening; (2) It will be important to determine the function of these tumor-associated trisialylated glycoproteins.