Cell Surface Sialic Acid Modulates Extracellular Matrix Adhesion and Migration in Pancreatic Adenocarcinoma Cells

Bassagañas, Sònia; Pérez-Garay, Marta; Peracaula, Rosa

doi:10.1097/mpa.0b013e31829d9090

Cited by 41 publications

(39 citation statements)

References 44 publications

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“…We had previously described that the levels of α2 subunit found in the MDAPanc-28 model were extremely low compared to Capan-1 model [30], what precluded further analysis of the α2β1 integrin glycosylation pattern influence on collagen type 1 adhesion using the MDAPanc-28 cell model. The corresponding study was then conducted with CP and C31 cells.…”

Section: Resultsmentioning

confidence: 98%

“…Human pancreatic adenocarcinoma cell lines Capan-1 (ATCC n°HTB-79; MD, USA) and MDAPanc-28, and the described stable ST3Gal III transfected (C31 and M34, respectively) and mock transfected (CP and MP, respectively) [23], [30] were used in this work. Cells were cultured in Dulbecco's Modified Eagle's Medium (DMEM) GlutaMAX-I containing 10% Fetal Bovine Serum (FBS), 100 U/mL Penicillin G, 100 mg/mL Streptomycin, 0.25 mg/mL Amphotericin B, and supplemented with 400 µg/ml (Capan-1 transfectants) or 800 µg/ml (MDAPanc-28 transfectants) Geneticine G-418 (all of them from Gibco, UK), under a humidified atmosphere containing 5% CO 2 .…”

Section: Methodsmentioning

confidence: 99%

“…Cell adhesion assays were performed as previously described [30]. 96-well microplates were coated with a solution of 10 µg/ml type 1 collagen from calf skin (Sigma-Aldrich; MO, USA) in PBS, or PBS-1% BSA.…”

Section: Methodsmentioning

confidence: 99%

“…Cell migration was evaluated using modified Boyden chambers as previously described [23], [30]. Briefly, serum starved cells were detached, resuspended in serum-free medium and seeded onto type 1 collagen coated inserts (Greiner Bio-One GmbH; Austria) containing DMEM-1% FBS.…”

Section: Methodsmentioning

confidence: 99%

“…ST3Gal III transfectants exhibited loss of cell-ECM adhesion, increased motility rates through type 1 collagen and an enhanced metastatic phenotype in vivo [23], [30]. To understand this enhanced metastatic phenotype in vivo , we here address whether cell-cell adhesiveness and cell invasion are also affected by the cell sialylation changes using the stably transfected cell line models.…”

Section: Introductionmentioning

confidence: 99%

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Pancreatic Cancer Cell Glycosylation Regulates Cell Adhesion and Invasion through the Modulation of α2β1 Integrin and E-Cadherin Function

et al. 2014

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In our previous studies we have described that ST3Gal III transfected pancreatic adenocarcinoma Capan-1 and MDAPanc-28 cells show increased membrane expression levels of sialyl-Lewis x (SLex) along with a concomitant decrease in α2,6-sialic acid compared to control cells. Here we have addressed the role of this glycosylation pattern in the functional properties of two glycoproteins involved in the processes of cancer cell invasion and migration, α2β1 integrin, the main receptor for type 1 collagen, and E-cadherin, responsible for cell-cell contacts and whose deregulation determines cell invasive capabilities. Our results demonstrate that ST3Gal III transfectants showed reduced cell-cell aggregation and increased invasive capacities. ST3Gal III transfected Capan-1 cells exhibited higher SLex and lower α2,6-sialic acid content on the glycans of their α2β1 integrin molecules. As a consequence, higher phosphorylation of focal adhesion kinase tyrosine 397, which is recognized as one of the first steps of integrin-derived signaling pathways, was observed in these cells upon adhesion to type 1 collagen. This molecular mechanism underlies the increased migration through collagen of these cells. In addition, the pancreatic adenocarcinoma cell lines as well as human pancreatic tumor tissues showed colocalization of SLex and E-cadherin, which was higher in the ST3Gal III transfectants. In conclusion, changes in the sialylation pattern of α2β1 integrin and E-cadherin appear to influence the functional role of these two glycoproteins supporting the role of these glycans as an underlying mechanism regulating pancreatic cancer cell adhesion and invasion.

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Section: Resultsmentioning

confidence: 98%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Pancreatic Cancer Cell Glycosylation Regulates Cell Adhesion and Invasion through the Modulation of α2β1 Integrin and E-Cadherin Function

et al. 2014

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Surfaceome: a new era in the discovery of immune evasion mechanisms of circulating tumor cells

Masmoudi,

Vialaret,

Hirtz

et al. 2024

Molecular Oncology

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Circulating tumor cells (CTCs) are cancer cells that detach from the original site and reach the bloodstream. The most aggressive CTCs survive various immune system attacks and initiate metastasis formation. Importantly, CTCs are not specifically targeted by the current immunotherapies due to the limited knowledge on specific targets. Proteomic profiling can be a powerful tool for understanding some of the immune evasion mechanisms used by cancer cells and particularly CTCs. These mechanisms are generally linked to the expression of specific surface proteins/peptides (i.e. the surfaceome). The study of the peptides that bind to class I molecules of the major histocompatibility complex (MHC‐I) and of the various glycoproteins expressed on CTC surface may open a completely new avenue for the discovery of novel mechanisms of immune evasion. In this review, we discuss how immunopeptidomic and glycoproteomic studies of CTCs that interact with immune cells could help to better understand how metastasis‐initiator CTCs escape the host immune response. We also describe how immunopeptidomic and glycoproteomic studies are carried out.

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Sialylation acts as a checkpoint for innate immune responses in the central nervous system

Klaus

Liao

Allendorf

et al. 2020

Glia

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Sialic acids are monosaccharides that normally terminate the glycan chains of cell surface glyco‐proteins and ‐lipids in mammals, and are highly enriched in the central nervous tissue. Sialic acids are conjugated to proteins and lipids (termed “sialylation”) by specific sialyltransferases, and are removed (“desialylation”) by neuraminidases. Cell surface sialic acids are sensed by complement factor H (FH) to inhibit complement activation or by sialic acid‐binding immunoglobulin‐like lectin (SIGLEC) receptors to inhibit microglial activation, phagocytosis, and oxidative burst. In contrast, desialylation of cells enables binding of the opsonins C1, calreticulin, galectin‐3, and collectins, stimulating phagocytosis of such cells. Hypersialylation is used by bacteria and cancers as camouflage to escape immune recognition, while polysialylation of neurons protects synapses and neurogenesis. Insufficient lysosomal cleavage of sialylated molecules can lead to lysosomal accumulation of lipids and aggregated proteins, which if excessive may be expelled into the extracellular space. On the other hand, desialylation of immune receptors can activate them or trigger removal of proteins. Loss of inhibitory SIGLECs or FH triggers reduced clearance of aggregates, oxidative brain damage and complement‐mediated retinal damage. Thus, cell surface sialylation recognized by FH, SIGLEC, and other immune‐related receptors acts as a major checkpoint inhibitor of innate immune responses in the central nervous system, while excessive cleavage of sialic acid residues and consequently removing this checkpoint inhibitor may trigger lipid accumulation, protein aggregation, inflammation, and neurodegeneration.

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Cell Surface Sialic Acid Modulates Extracellular Matrix Adhesion and Migration in Pancreatic Adenocarcinoma Cells

Abstract: This study shows how the intrinsic heterogeneity of cell membrane sialylation regulates the adhesive and migratory potential of pancreatic adenocarcinoma cells.

Cited by 41 publications

References 44 publications

Pancreatic Cancer Cell Glycosylation Regulates Cell Adhesion and Invasion through the Modulation of α2β1 Integrin and E-Cadherin Function

Pancreatic Cancer Cell Glycosylation Regulates Cell Adhesion and Invasion through the Modulation of α2β1 Integrin and E-Cadherin Function

Surfaceome: a new era in the discovery of immune evasion mechanisms of circulating tumor cells

Sialylation acts as a checkpoint for innate immune responses in the central nervous system

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