Transforming growth factor-β challenge alters the N-, O-, and glycosphingolipid glycomes in PaTu-S pancreatic adenocarcinoma cells

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is characterized by poor prognosis and high mortality. Transforming growth factor-β (TGF-β) plays a key role in PDAC tumor progression, which is often associated with aberrant glycosylation. However, how PDAC cells respond to TGF-β and the role of glycosylation therein is not well known. Here, we investigated the TGF-β-mediated response and glycosylation changes in the PaTu-8955S (PaTu-S) cell line deficient in SMA-related and MAD-related protein 4 (SMAD4), a signal transducer of the TGF-β signaling. PaTu-S cells responded to TGF-β by upregulating SMAD2 phosphorylation and target gene expression. We found that TGF-β induced expression of the mesenchymal marker N-cadherin but did not significantly affect epithelial marker E-cadherin expression. We also examined differences in N-glycans, O-glycans, and glycosphingolipid-linked glycans in PaTu-S cells upon TGF-β stimulation. TGF-β treatment primarily induced N-glycome aberrations involving elevated levels of branching, core fucosylation, and sialylation in PaTu-S cells, in agreement with TGF-β-induced changes in the expression of glycosylation-associated genes. In addition, we observed differences in O glycosylation and glycosphingolipid glycosylation profiles after TGF-β treatment, including lower levels of sialylated Tn antigen and neoexpression of globosides. Furthermore, the expression of transcription factor sex-determining region Y-related high-mobility group box 4 was upregulated upon TGF-β stimulation, and its depletion blocked TGF-β-induced N-glycomic changes. Thus, TGF-β-induced N-glycosylation changes can occur in a sex-determining region Y-related high-mobility group box 4–dependent and SMAD4-independent manner in the pancreatic PaTu-S cancer cell line. Our results open up avenues to study the relevance of glycosylation in TGF-β signaling in SMAD4-inactivated PDAC. Pancreatic ductal adenocarcinoma (PDAC) is characterized by poor prognosis and high mortality. Transforming growth factor-β (TGF-β) plays a key role in PDAC tumor progression, which is often associated with aberrant glycosylation. However, how PDAC cells respond to TGF-β and the role of glycosylation therein is not well known. Here, we investigated the TGF-β-mediated response and glycosylation changes in the PaTu-8955S (PaTu-S) cell line deficient in SMA-related and MAD-related protein 4 (SMAD4), a signal transducer of the TGF-β signaling. PaTu-S cells responded to TGF-β by upregulating SMAD2 phosphorylation and target gene expression. We found that TGF-β induced expression of the mesenchymal marker N-cadherin but did not significantly affect epithelial marker E-cadherin expression. We also examined differences in N-glycans, O-glycans, and glycosphingolipid-linked glycans in PaTu-S cells upon TGF-β stimulation. TGF-β treatment primarily induced N-glycome aberrations involving elevated levels of branching, core fucosylation, and sialylation in PaTu-S cells, in agreement with TGF-β-induced changes in the expression of glycosylation-associated genes. In addition, we observed differences in O glycosylation and glycosphingolipid glycosylation profiles after TGF-β treatment, including lower levels of sialylated Tn antigen and neoexpression of globosides. Furthermore, the expression of transcription factor sex-determining region Y-related high-mobility group box 4 was upregulated upon TGF-β stimulation, and its depletion blocked TGF-β-induced N-glycomic changes. Thus, TGF-β-induced N-glycosylation changes can occur in a sex-determining region Y-related high-mobility group box 4–dependent and SMAD4-independent manner in the pancreatic PaTu-S cancer cell line. Our results open up avenues to study the relevance of glycosylation in TGF-β signaling in SMAD4-inactivated PDAC. Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal tumors in the world. It is characterized by a poor prognosis and a failure to respond to therapy (1Siegel R.L. Miller K.D. Jemal A. Cancer statistics, 2019.CA Cancer J. Clin. 2019; 69: 7-34Google Scholar). Genomic analysis of PDAC revealed that the most frequent genetic alterations include the activation of oncogene KRAS and inactivation of the tumor suppressors tumor protein p53 (TP53), SMA-related and MAD-related protein 4 (SMAD4), and cyclin-dependent kinase inhibitor 2A (CDKN2A) (2Vincent A. Herman J. Schulick R. Hruban R.H. Goggins M. Pancreatic cancer.Lancet. 2011; 378: 607-620Google Scholar, 3Jones S. Zhang X. Parsons D.W. Lin J.C. Leary R.J. Angenendt P. Mankoo P. Carter H. Kamiyama H. Jimeno A. Hong S.M. Fu B. Lin M.T. Calhoun E.S. Kamiyama M. et al.Core signaling pathways in human pancreatic cancers revealed by global genomic analyses.Science. 2008; 321: 1801-1806Google Scholar, 4Pan S. Brentnall T.A. Chen R. Proteome alterations in pancreatic ductal adenocarcinoma.Cancer Lett. 2020; 469: 429-436Google Scholar). The accumulation of these genetic mutations contributes to the stepwise progression of PDAC. KRAS mutations occur in the early stage of PDAC (5Fischer C.G. Wood L.D. From somatic mutation to early detection: Insights from molecular characterization of pancreatic cancer precursor lesions.J. Pathol. 2018; 246: 395-404Google Scholar), whereas mutations of TP53, SMAD4, and CDKN2A arise in advanced pancreatic intraepithelial and pancreatic M. J. R. pancreatic and Scholar, R.H. A. Goggins M. pancreatic intraepithelial J. Clin. Pathol. 2008; Scholar, M. Zhang alterations associated with progression from pancreatic intraepithelial to pancreatic Scholar). genetic can protein and signaling pathways to cell S. M. B. M. M. A. S. B. et of signaling pancreatic cell and Scholar, E.S. J.C. A. M. B. et is pancreatic Scholar), J. A. a target in pancreatic and 2020; Scholar), J. H. H. M. expression of growth factor in human pancreatic cancer with Cancer Scholar, M. R. B. M. A. S. expression of growth factor early and poor prognosis after ductal adenocarcinoma of the Scholar), R. S. S. J. R. Brentnall T.A. Pancreatic cancer The that and Scholar), S. S. Leary R. Fu B. Kamiyama M. Hruban R.H. B. the genetic of pancreatic Scholar), and S. H. X. alterations and therapy in pancreatic ductal 2020; Scholar, H. pancreatic ductal and 2018; Scholar). The growth factor-β (TGF-β) signaling is in cell and to including cancer S. P. TGF-β signaling in Scholar, J. Transforming growth factor-β signaling in and 2019; Scholar). TGF-β is a which by to cell TGF-β and that and TGF-β with is and a is J. cells TGF-β Scholar, J. in Scholar). the kinase the and of and the signal is the P. TGF-β from cell to Scholar). signaling by the phosphorylation of that SMAD2 and can with the that SMAD4, which the to the transcription of target R. Transforming growth factor-β and and Scholar). is a of TGF-β-induced growth A. A. J. and in TGF-β Scholar, X. We R. R. of the TGF-β and of TGF-β-mediated Scholar), which results in its role a tumor the early of cancer However, the of signaling is in of of the inactivation of J. A. P. A. and the in with pancreatic ductal J. 2020; Scholar). The gene mutation can to the of which of the signaling TGF-β can and SMAD4-independent in that can with sex-determining region Y-related high-mobility group box 4 transcription which with with A. A. can TGF-β-mediated in a manner to 2018; Scholar, S. H. and gene Scholar). The transcription and in the the expression of TGF-β target and A. A. can TGF-β-mediated in a manner to 2018; Scholar, S. H. and gene Scholar, Chen M. J. J. TGF-β tumor a lethal Scholar, J. M. X. J. Zhang H. J. B. and contributes to cancer Scholar). In addition, can signal signaling the protein kinase signaling including the kinase and pathways well the signaling pathways of the TGF-β Scholar, J. S.M. R. TGF-β kinase phosphorylation of J. Scholar, M. R. activation of a kinase by signaling and in tumor Scholar, P. P. M. is a of a signaling that S. A. 2008; Scholar, A. TGF-β Scholar). The and signaling pathways in including TGF-β-induced M. X. Zhang activation of and by 2008; Scholar, A. A. A. P. TGF-β signaling and cancer Scholar). is a cell which the epithelial cells and and mesenchymal and R. and the 2019; Scholar). can associated with changes by a in the expression of marker a of epithelial and of mesenchymal including and A. of Clin. Scholar, S. R. TGF-β signaling and in cancer Scholar). is a and and cells can a a The is to the cells J. P. M. A. J. S. R. J. A. et and 2020; Scholar). and in and the is to in cell and in the of of tumor cells and in 2020; Scholar). the TGF-β signaling in the of in PDAC cells to a TGF-β-induced lethal by cell that from to Chen M. J. J. TGF-β tumor a lethal Scholar). of and is a in cells, which cell and in and Scholar, J. The glycosylation of pancreatic Lett. 2019; Scholar). glycosylation is associated with TGF-β signaling and TGF-β-induced in cancers J. P. M. Zhang of glycosylation in TGF-β signaling and in by the of TGF-β of in the of to Scholar), in cells, and with TGF-β J. TGF-β is by glycosylation of the TGF-β J. Scholar). and in the of N-glycans, O-glycans, and glycosphingolipid glycans TGF-β-induced in cancers X. X. Chen S. of glycans in cancer cells Scholar), cancer M. Chen H. Zhang J. and of cell cancer J. and cancer X. X. Chen S. of glycans in cancer cells Scholar, M. J. of in induced by growth factor in epithelial cell Scholar). PDAC progression, aberrant glycosylation is with S. Brentnall T.A. Chen R. Proteome alterations in pancreatic ductal adenocarcinoma.Cancer Lett. 2020; 469: 429-436Google Scholar, M. J. glycosylation and cancer and 2019; Scholar). a of glycosylation including and sialylation in pancreatic cancer progression in The and of alterations in pancreatic cancer revealed Scholar, J. glycosylation of pancreatic cancer with Proteome Scholar). The glycosylation changes of growth factor protein and protein in signaling including tumor and pathways S. Chen R. Brentnall T.A. analysis changes in N-glycosylation associated with pancreatic ductal Proteome Scholar, Chen R. Brentnall T.A. S. of protein in pancreatic Clin. Scholar). In addition, the one of the that the in can the growth of pancreatic cells R.L. A. of pancreatic cancer cell 2011; Scholar). aberrations in glycosylation the of and to cell and A. P. role of Scholar, of the key in cancer marker 2011; Scholar, R. and of in Scholar, and in J. Scholar). the cancer antigen to the the and early of pancreatic cancer J. H. Zhang H. Chen and in the of pancreatic J. Clin. Scholar, H. K.D. A. S. B. B. B. B. et and pancreatic cancer in 2019; Scholar, A. J. P. H. M. J. M. of and the in with pancreatic Clin. Pathol. Scholar, S. A. J. J. M.T. pancreatic cancer by Proteome Scholar). of the aberrant glycosylation of PDAC induced by TGF-β the of and However, the molecular of TGF-β signaling in PDAC cells and to glycosylation not well In the (PaTu-S) cell a human PDAC cell line KRAS activation and inactivation of and was to TGF-β and glycosylation changes. TGF-β treatment, PaTu-S cells gene of epithelial and of mesenchymal by analysis of glycosylation-associated with we the TGF-β-induced alterations in the of cell glycans of N-glycans, O-glycans, and Furthermore, we investigated the role of in TGF-β signaling and TGF-β-induced glycosylation in PaTu-S a how glycosylation alterations to TGF-β-mediated of PDAC. the PaTu-S cell which SMAD4, is to TGF-β treatment we analysis of SMAD2 levels of PaTu-S cells and with TGF-β In PaTu-S cells, SMAD2 phosphorylation was significantly upregulated upon TGF-β which was blocked by treatment with kinase inhibitor The expression of TGF-β target including factor P. A. P. S. role of and TGF-β signaling in 2011; Scholar, R. S. R. of by p53 and Scholar), S. S. P. S. of and to in the of human J. Scholar, R. of and signaling in inhibitor gene expression in 2008; Scholar), S.M. S. M. T.A. Transforming growth factor-β protein and and protein kinase signaling Scholar), and A. P. R. TGF-β of the gene and the Scholar), was induced by TGF-β treatment can induced by and pathways and in cells in which was of growth factor (TGF-β) target and TGF-β-induced from its and Scholar). In response to TGF-β the PaTu-S cells in the expression of the epithelial marker gene the protein and the mesenchymal marker the protein the protein and the protein the protein the mesenchymal marker N-cadherin was after TGF-β stimulation, whereas E-cadherin and expression levels not significantly In addition, changes of PaTu-S cells observed after of TGF-β treatment treatment not The response of PaTu-S cells to TGF-β treatment was by of E-cadherin and We observed that TGF-β induced in the of and and the of cells However, in response to changes in E-cadherin expression and of to in cell M. A. cell and the of Scholar), we examined the TGF-β response of PaTu-S cells and The PaTu-S cells with TGF-β and a of cells the of 4 we observed of cell cells in one in the in the TGF-β group with the Thus, TGF-β the of PaTu-S cells in these results that the PaTu-S cells responded to TGF-β with of SMAD2 phosphorylation and target gene expression. In addition, upon TGF-β treatment, in mesenchymal marker expression was observed but a in of epithelial TGF-β treatment of PaTu-S the in and cell in in glycosylation of and cell including TGF-β signaling. of these pathways associated with that cancer progression J. P. M. Zhang of glycosylation in TGF-β signaling and in Scholar). by the of TGF-β PaTu-S cell we investigated the glycosylation of PaTu-S upon TGF-β We a analysis of N-glycans, O-glycans, and one the analysis of and S. Zhang J. P. M. of a and 2020; and the the analysis of the analysis of we in the M. the characterization of glycans from from and Scholar, analysis of and from Scholar). the of the and which in and of with and TGF-β treatment was and in and by expression levels of glycosylation-associated in the to the of the and to the to of from the investigated In agreement with analysis of PaTu-S cell S. M. of pancreatic cancer cells in Scholar), the N-glycome of PaTu-S found to with of and and of and of the and In addition, of The primarily with also in TGF-β treatment, N-glycosylation changes and of the N-glycome after TGF-β treatment in to in from to with TGF-β treatment which is by the and in with the of and that in the of N-glycans, upon TGF-β treatment and 4 and sialylation was high in PaTu-S cells after TGF-β treatment with a with which is in line with the expression of and and In addition, a of core was observed in line with the of and TGF-β treatment induced a of from to in the PaTu-S cell line a of the and glycosylation-associated gene expression the we with The of core and core with levels of core 4 also high of sialylation was observed in O-glycans, whereas of the The profiles in PaTu-S cells and cells a and changes. in core was observed with a in core from the of and and lower of Tn antigen was upon TGF-β treatment which is in line with the and a of sialylation of from to was observed in with the elevated levels of and and in to the sialylation differences of the N-glycome In sialylation of sialylation of of was we of sialylation of PaTu-S cells with and TGF-β the of and and a of the and glycosylation-associated gene expression glycans after of the group from from PaTu-S profiles upon TGF-β treatment the which to induced by the treatment, with expression levels with the and and including and in PaTu-S cells after TGF-β treatment, was in the with the upon TGF-β treatment, gene of also a expression of which is the key gene the of and the expression levels of after TGF-β 4 and was in and a of the and gene expression is a key target of the TGF-β signaling A. A. can TGF-β-mediated in a manner to 2018; in cell including epithelial cells R. TGF-β-induced expression of mesenchymal cell epithelial to mesenchymal Scholar), cells H. M. TGF-β signaling of cells Scholar), and pancreatic cancers Chen M. J. J. TGF-β tumor a lethal Scholar). is induced by TGF-β in SMAD4-independent manner and in PDAC cells Chen M. J. J. TGF-β tumor a lethal Scholar). we found that and protein expression levels upregulated in PaTu-S cells upon TGF-β and 4 the role of in the TGF-β-induced changes in we the in PaTu-S of was significantly the and protein levels in by TGF-β was by the depletion The was by the expression of the target and Chen M. J. J. TGF-β tumor a lethal Scholar). TGF-β-induced of including and was by depletion and the of and did not with depletion after TGF-β treatment and The was observed in a of the lower expression of and in the cells with the group in the of TGF-β and The TGF-β-induced in core was by in PaTu-S cells well the of expression and and and results by depletion in TGF-β-induced of we to that by and revealed the expression of the gene and protein in cells and TGF-β-induced in well the gene expression levels including and by depletion and the of core with TGF-β was from the expression of the gene by and depletion also significantly the of sialylation and expression levels of associated that and and results that is a TGF-β signaling in the PaTu-S cell line. plays a key role in the TGF-β-mediated glycosylation in in the levels of branching, and core the In addition, we study to pancreatic adenocarcinoma cell and cells S. TGF-β-induced of and in cancer cell Scholar). with the results with PaTu-S cells, we observed that TGF-β induced levels in and cells response was in cells, and cells treatment of cells with TGF-β target and found to upregulated TGF-β induced the expression of mesenchymal including and the but the protein expression of N-cadherin was by TGF-β in cells and The results with to the results we PaTu-S However, the including and induced by TGF-β treatment 4 Thus, the response to TGF-β in cells is that in PaTu-S the role of in cells, we the with in cells and the by and and The TGF-β-induced of and was by Thus, plays a role in TGF-β-mediated of in PDAC Here, we a analysis of TGF-β-induced and in PaTu-S pancreatic adenocarcinoma Our study the of branching, and core of in PaTu-S cells in SMAD4-independent N-glycosylation changes found to by changes of the genes. that TGF-β-mediated N-glycosylation changes in the signaling but in SMAD4-independent and its including significantly in the epithelial cell which the cell and J. S. J. growth Scholar). In the of gene expression and sialylation was observed in the PaTu-S cell line. Thus, to the role of these glycosylation changes TGF-β in PDAC. In addition, the of by TGF-β treatment, which is of SMAD4, in the PaTu-S cell line in of glycans sialylation of and core the sialylated Tn antigen was by TGF-β in cells, which is by and is associated with cancer progression, and in of the cell by sialylated Scholar, J. The role of in J. Scholar). In line with TGF-β-induced we also observed the of sialylated Tn antigen in the cells B. Zhang J. P. M. and glycosphingolipid glycosylation in human pancreatic adenocarcinoma cells with and 2020; Scholar), which was from the the PaTu-S cell line. results a role of sialylated Tn antigen in TGF-β signaling and response in the PaTu-S cell line. to in the TGF-β-induced in of human and epithelial cell S. A. and human cells in the of human epithelial J. Scholar), of which The of TGF-β-induced and cell and by including and in the TGF-β In the PaTu-S cell the differences the expression of and the of upon TGF-β stimulation. that gene expression not in of protein R. of protein and expression Scholar, M. of and protein in Lett. Scholar). The neoexpression of TGF-β treatment is to associated with tumor and in including cancer M. H. A. of of by inhibitor of and its of Scholar), cancer R. B. A. M. The glycosphingolipid in the of S. A. Scholar, M. M. X. S. tumors and and can by Cancer 2008; Scholar), cancer S. S. J. cancer and and can by Scholar), adenocarcinoma M. M. A. J. A. the glycosphingolipid of cancer cells with Cancer Scholar), and pancreatic cancer M. J. M. H. J. glycosphingolipid expression and of human pancreatic ductal of and Scholar). In addition, a key can and in cancer cells M. of and protein in Lett. Scholar). In and in the cells with epithelial PaTu-S cells B. Zhang J. P. M. and glycosphingolipid glycosylation in human pancreatic adenocarcinoma cells with and 2020; Scholar). these that the to the and in PDAC. In the of to the role of sialylated Tn antigen and in TGF-β-mediated PDAC we that a TGF-β target is TGF-β-induced in of in PaTu-S cells in the of TGF-β-mediated in and core was to in PDAC cells of expression Chen M. J. J. TGF-β tumor a lethal Scholar), to the glycosylation changes and in study that the signaling tumor in cancer cells A. S. P. J. A. P. M. A. J. et in Scholar). Our study of glycosylation in PaTu-S cells revealed that these cells to cells and which the response B. Zhang J. P. M. and glycosphingolipid glycosylation in human pancreatic adenocarcinoma cells with and 2020; Scholar). Thus, the signaling of N-glycosylation branching, and core in PaTu-S We results PaTu-S cells to include PDAC that We found a response to and that depletion the TGF-β-induced in in cells In of the phosphorylation of the upon TGF-β in PDAC we found that TGF-β can significantly the expression of TGF-β target including and in PaTu-S and cell of TGF-β target that not which a of M. M.T. H. R. H. of gene expression a Scholar), of TGF-β target upon in human cells of growth factor (TGF-β) target and TGF-β-induced from its and Scholar). TGF-β target and not by the gene was in the of in study of growth factor (TGF-β) target and TGF-β-induced from its and Scholar), the also that gene a with TGF-β after of growth factor (TGF-β) target and TGF-β-induced from its and Scholar). The study also that the gene expression of the protein can induced by the of phosphorylation and transducer and of transcription activation in cells H. J. S. A. H. S. P. Transforming growth factor-β growth factor expression in cells signaling Scholar). that TGF-β target can by and SMAD4-independent Our the TGF-β-induced changes in gene expression in the PaTu-S and cell we found that the TGF-β-mediated of target and in PaTu-S cells that expression of these TGF-β-induced target is in SMAD4-independent and We investigated the changes in expression of upon TGF-β treatment the gene and protein levels in PaTu-S and N-cadherin by the by the and by the induced by TGF-β treatment the the protein N-cadherin not and not was upregulated in response to TGF-β and 4 in PaTu-S and In addition, expression and of the epithelial marker E-cadherin by TGF-β after and 4 of Our results that these cell including the PaTu-S and cell not a TGF-β-induced results also in the study Chen M. J. J. TGF-β tumor a lethal that cells E-cadherin expression after TGF-β treatment In addition, we found that TGF-β in PaTu-S cells, of the and a TGF-β to of the and TGF-β signaling B. R. A. Transforming growth factor of and by kinase and to the 69: Scholar, A. P. A. J. M. TGF-β a Scholar, S. The growth factor signaling and cell by the and the 2008; Scholar). In human cells, TGF-β treatment induced a of the signaling which the activation of the including and S. M. P. Transforming growth of signaling by and Scholar). Thus, the of the role of glycosylation in TGF-β-induced in PaTu-S cells to how TGF-β in the and also a and from was from was by A. of and from and and and from of with high from and from The from was from was from and was from from and in and and from was and from a The of human and that to the expression of in The that and E-cadherin and N-cadherin and PaTu-S cell line was from B. and of cell with of from one human pancreatic Pathol. Pathol. Scholar). pancreatic adenocarcinoma and cell from and cells in with and cells in and with and cell the of and by the in the PaTu-S cells in with The of TGF-β was and the of and was a with and and 4 4 the protein the protein of the by and protein analysis was by and and with the with and results the to the from the The was with of with in levels to target gene expression. the changes of including and 4 to the gene expression with TGF-β and 4 and of The human the and with the The and in The was a to and from The was from from We the most PaTu-S cells with and with a of target but the a in its the of cells, we including and The was a not by cells with and that protein of the and R. H. P. is by phosphorylation and TGF-β Scholar). The and a to of cell we a of the in with of PaTu-S cells cells with the a cell cells with of in to the The PaTu-S cells with and a that was by cell high expression. high cells and and was cells with and with with TGF-β and 4 the cells with and with The cells blocked with in with the of E-cadherin in was to cells of with the of and was to the cells the cells with and with with by the in and results We the The to the by the of was J. S. P. of human cancer cells in Scholar). In PaTu-S cells with TGF-β and cells the of the the 4 after The is a the and the with and by The of cell cells a the in the region was and from PaTu-S cells a S. Zhang J. P. M. of a and 2020; Scholar, B. Zhang J. P. M. and glycosphingolipid glycosylation in human pancreatic adenocarcinoma cells with and 2020; Scholar). In from cells to the in a was by and in by and in a box the was by The was by of with to to well and from the by and the of the by of and in a and by a S. Zhang J. P. M. of a and 2020; Scholar, analysis of and from Scholar). in a in and in of to of N-glycans, the from the of in was well after with of a and in a box to by The by of and with of with a to to the to in a of was to the by to the the of the The and The in of to of and of from PaTu-S cells in B. Zhang J. P. M. and glycosphingolipid glycosylation in human pancreatic adenocarcinoma cells with and 2020; Scholar). cells and with of The cell by and was to the by of was to the cell and 4 with The was after of was by of and the was and to the The of and the was In the was and by the of The in the of the the in and by the of with of and of by with The to the and with The from the with and The the and in the glycans from the a of and was to and The glycans and which with of and of The with of and glycans to the of was to the to the glycans from the The and and in The was with the in analysis of and from Scholar, B. Zhang J. P. M. and glycosphingolipid glycosylation in human pancreatic adenocarcinoma cells with and 2020; Scholar). In glycans to in of in of was to the and the The of glycans was with of The and and in The was and the in of to The analysis of was a S. Zhang J. P. M. of a and 2020; Scholar, B. Zhang J. P. M. and glycosphingolipid glycosylation in human pancreatic adenocarcinoma cells with and 2020; Scholar). with a and a to of whereas was The was with from whereas the was with from and was the a in was with a of to in and to in and to by a of a of a from to was a The was a of was the with a of and a of and of to N-glycans, to O-glycans, and to glycans in was to and the of glycans by in Zhang S. M. cancer cell of the 2020; Scholar). the of the in M. the characterization of glycans from from and Scholar, P. H. Scholar, of by Scholar), and with the of A. H. R. A. S.M. the of of Proteome 2008; and glycosylation from of glycans was by the of glycans one to of by the of the by the of to the of is is is is is and is with a The from and the the is by in the and was The that the of study in in with the the The that of with the of We and the of the PaTu-S cell line and We the and of the J. S. M. P. and J. S. M. P. and J. and B. and J. M. P. and M. P. and J. and was by the to J. Cancer to P. and to B.

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