Lewis x is highly expressed in normal tissues: A comparative immunohistochemical study and literature revision

Croce, María Virginia; Isla-Larrain, M.; Rabassa, Martín Enrique; Demichelis, Sandra O.; Colussi, A.; M, Crespo; Lacunza, Ezequiel; Segal‐Eiras, Amada

doi:10.1007/bf02893488

Cited by 43 publications

(33 citation statements)

References 67 publications

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“…sLe glycans are normally present on leukocytes and are critical in leukocyte adhesion and extravasation during an inflammatory response. Conversely, sLe expression is typically low in non-cancerous epithelial cells [19, 155]. sLe structures are tetrasaccharides composed of a GlcNAc-Gal backbone with an α2-3-linked sialic acid attached to Gal, and fucose linked to GlcNAc (Fig.…”

Section: Sialyl Lewis Structures In Tumor Disseminationmentioning

confidence: 99%

Regulation of the metastatic cell phenotype by sialylated glycans

Schultz

Swindall

Bellis

2012

Cancer Metastasis Rev

278

261

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Section: Sialyl Lewis Structures In Tumor Disseminationmentioning

confidence: 99%

Regulation of the metastatic cell phenotype by sialylated glycans

Schultz

Swindall

Bellis

2012

Cancer Metastasis Rev

278

261

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“…MUC4 expression has been reported in a variety of well-differentiated epithelial tissues in the adult including gastrointestinal tract, breast [13,14], and lung [15,16]. MUC4 expression has also been reported in a variety of carcinomas including ovarian [17,18], lung [15,19], pancreatic [20,21], gall bladder [22], and breast [23].…”

Section: Introductionmentioning

confidence: 99%

The membrane mucin MUC4 is elevated in breast tumor lymph node metastases relative to matched primary tumors and confers aggressive properties to breast cancer cells

et al. 2009

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IntroductionPrevious studies indicate that overexpression of the membrane-associated mucin MUC4 is potently anti-adhesive to cultured tumor cells, and suppresses cellular apoptotic response to a variety of insults. Such observations raise the possibility that MUC4 expression could contribute to tumor progression or metastasis, but the potential involvement of MUC4 in breast cancer has not been rigorously assessed. The present study aimed to investigate the expression of the membrane mucin MUC4 in normal breast tissue, primary breast tumors and lymph node metastases, and to evaluate the role of MUC4 in promoting the malignant properties of breast tumor cells.MethodsMUC4 expression levels in patient-matched normal and tumor breast tissue was initially examined by immunoblotting lysates of fresh frozen tissue samples with a highly specific preparation of anti-MUC4 monoclonal antibody 1G8. Immunohistochemical analysis was then carried out using tissue microarrays encompassing patient-matched normal breast tissue and primary tumors, and patient-matched lymph node metastases and primary tumors. Finally, shRNA-mediated knockdown was employed to assess the contribution of MUC4 to the cellular growth and malignancy properties of JIMT-1 breast cancer cells.ResultsImmunoblotting and immunohistochemistry revealed that MUC4 levels are suppressed in the majority (58%, p < 0.001) of primary tumors relative to patient-matched normal tissue. On the other hand, lymph node metastatic lesions from 37% (p < 0.05) of patients expressed higher MUC4 protein levels than patient-matched primary tumors. MUC4-positive tumor emboli were often found in lymphovascular spaces of lymph node metastatic lesions. shRNA-mediated MUC4 knockdown compromised the migration, proliferation and anoikis resistance of JIMT-1 cells, strongly suggesting that MUC4 expression actively contributes to cellular properties associated with breast tumor metastasis.ConclusionsOur observations suggest that after an initial loss of MUC4 levels during the transition of normal breast tissue to primary tumor, the re-establishment of elevated MUC4 levels confers an advantage to metastasizing breast tumor cells by promoting the acquisition of cellular properties associated with malignancy.

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“…The most prominent member of this family in humans is the 5-acetylated version known as Neu5Ac (5- N -acetylneuraminic acid). This sugar is present as the terminal moiety of a range of human glycoproteins, such as TLRs (Toll-like receptors) [11], integrins [12], mucins [9] and the blood group antigens SLeX/SLeA (sialyl-Lewis A/sialyl-Lewis X) [13]. Most commonly, it is linked to underlying sugars via α-2,3 or α-2,6 glycosidic linkages that are targeted by secreted or cell-associated sialidase enzymes from several members of the Bacteroidetes and other important human commensals and pathogens [8,9].…”

Section: Introductionmentioning

confidence: 99%

Structural and functional characterization of NanU, a novel high-affinity sialic acid-inducible binding protein of oral and gut-dwelling Bacteroidetes species

Phansopa

Roy

Rafferty

et al. 2014

Biochemical Journal

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Many human-dwelling bacteria acquire sialic acid for growth or surface display. We identified previously a sialic acid utilization operon in Tannerella forsythia that includes a novel outer membrane sialic acid-transport system (NanOU), where NanO (neuraminate outer membrane permease) is a putative TonBdependent receptor and NanU (extracellular neuraminate uptake protein) is a predicted SusD family protein. Using heterologous complementation of nanOU genes into an Escherichia coli strain devoid of outer membrane sialic acid permeases, we show that the nanOU system from the gut bacterium Bacteroides fragilis is functional and demonstrate its dependence on TonB for function. We also show that nanU is required for maximal function of the transport system and that it is expressed in a sialic acid-responsive manner. We also show its cellular localization to the outer membrane using fractionation and immunofluorescence experiments. Ligand-binding studies revealed high-affinity binding of sialic acid to NanU (K d ∼ 400 nM) from two Bacteroidetes species as well as binding of a range of sialic acid analogues. Determination of the crystal structure of NanU revealed a monomeric SusD-like structure containing a novel motif characterized by an extended kinked helix that might determine sugar-binding specificity. The results of the present study characterize the first bacterial extracellular sialic acid-binding protein and define a sialic acidspecific PUL (polysaccharide utilization locus).

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Lewis x is highly expressed in normal tissues: A comparative immunohistochemical study and literature revision

Cited by 43 publications

References 67 publications

Regulation of the metastatic cell phenotype by sialylated glycans

Regulation of the metastatic cell phenotype by sialylated glycans

The membrane mucin MUC4 is elevated in breast tumor lymph node metastases relative to matched primary tumors and confers aggressive properties to breast cancer cells

Structural and functional characterization of NanU, a novel high-affinity sialic acid-inducible binding protein of oral and gut-dwelling Bacteroidetes species

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