Tissue and serum α2-3- and α2-6-linkage specific sialylation changes in oral carcinogenesis

Abstract

Increased sialylation of cell surface glycoconjugates is among the key molecular changes associated with malignant transformation and cancer progression. We investigated significance of linkage-specific sialylation changes in oral carcinogenesis. Tissue and serum levels of total sialic acid (TSA), linkage-specific sialyltransferases (ST) and sialoproteins were analyzed from patients with oral precancerous conditions (OPC) and oral cancer as well as the post-treatment follow-up blood samples of oral cancer patients. TSA levels were measured using a spectrophotometric method. The linkage-specific lectins, Sambusus nigra (SNA) and Maackia amurensis (MAM) detects alpha 2-6- and alpha 2-3-linked sialic acid, respectively, were used to analyze ST activity and sialoproteins. Malignant tissues showed significantly higher levels of TSA, reactivity of SNA and MAM, and alpha 2,3-ST activity compared to the adjacent normal tissues. alpha 2,6-ST was also higher in malignant tissues. Similarly, the marker levels were higher in precancerous tissues than their adjacent normal tissues. Serum levels of TSA, TSA/ total proteins, alpha 2-6-sialoproteins and alpha 2,6-ST were markedly increased in untreated oral cancer patients compared to the controls and OPC as well as responder (CR) patients. Serum levels of the markers were higher or comparable between untreated oral cancer patients and non-responders (NR). Serum levels of alpha 2-3-sialylation were elevated in non-responders compared with the responders. Further, the observed sialylation changes in tissue and serum were found to be associated with various clinicopathological features and disease progression. Thus, the data suggest potential utility of sialylation markers in early detection, prognostication and treatment monitoring of oral cancer.

Expression of Glycosyltransferases; ST3GAL1, FUT3, FUT5, and FUT6 Transcripts in Oral Cancer

“…13,27 Alterations in enzyme activity of a-2,3 and a-2,6 STs, and FUT have been reported in serum of oral cancer patients. 7,8 However, there are no earlier reports on mRNA levels of ST and FUT in oral cancer.…”

“…[4][5][6] Previous studies from our laboratory have indicated elevated serum and tissue ST and FUT enzyme activities in oral cancer patients. 7,8 Elevations in serum and salivary sialic acid have been reported in oral cancer, which might be because of increase in ST or sialidase activities. 9 Various STs (ST3GAL, ST6GAL, ST6GALNAC, and ST8) are named according to the sialyl linkages they form.…”

“…19 Elevated levels of a-2,3 ST enzyme activity have been observed earlier in oral cancer patients. 7 However, the studies on its transcript levels (ST3GAL1) are lacking in oral cancer patients.…”

“…Earlier reports have documented elevations in ST and FUT enzyme activities in oral cancer patients. 7,8 However, the expressions of ST and FUT transcripts have not been explored in oral cancer patients. Therefore, present investigation aimed to evaluate clinical significance of mRNA expressions of ST3GAL1, FUT3, FUT5, and FUT6 in malignant and adjacent normal tissues obtained from oral cancer patients.…”

Sialic Acid and Sialyltransferase Activity in Serum and Tissues of Dogs With Mammary Tumors

“…4,16,[25][26][27][28] In humans, metastasizing tumors are characterized by an increased expression of Sia-a2,6, whereas benign tumors express mainly Sia-a2,3. Moreover, a higher activity of ST-a2,6 has been reported in malignant colorectal cells 5,9,35 and oral cancers 30 as well as in serum of patients with metastasizing tumors.…”