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PMID: 32911675 Published · epublish English Journal Article

The Sda Synthase B4GALNT2 Reduces Malignancy and Stemness in Colon Cancer Cell Lines Independently of Sialyl Lewis X Inhibition.

International journal of molecular sciences ·Vol. 21 ·No. 18 ·2020-09-08

Pucci M, Gomes Ferreira I, Malagolini N, Ferracin M, Dall'Olio F

Abstract

The Sda antigen and its biosynthetic enzyme B4GALNT2 are highly expressed in healthy colon but undergo a variable down-regulation in colon cancer. The biosynthesis of the malignancy-associated sialyl Lewis x (sLex) antigen in normal and cancerous colon is mediated by fucosyltransferase 6 (FUT6) and is mutually exclusive from that of Sda. It is thought that the reduced malignancy associated with high B4GALNT2 was due to sLex inhibition. We transfected the cell lines SW480 and SW620, derived respectively from a primary tumor and a metastasis of the same patient, with the cDNAs of FUT6 or B4GALNT2, generating cell variants expressing either the sLex or the Sda antigens. Transfectants were analyzed for growth in poor adherence, wound healing, stemness and gene expression profile. B4GALNT2/Sda expression down-regulated all malignancy-associated phenotypes in SW620 but only those associated with stemness in SW480. FUT6/sLex enhanced some malignancy-associated phenotypes in SW620, but had little effect in SW480. The impact on the transcriptome was stronger for FUT6 than for B4GALNT2 and only partially overlapping between SW480 and SW620. B4GALNT2/Sda inhibits the stemness-associated malignant phenotype, independently of sLex inhibition. The impact of glycosyltransferases on the phenotype and the transcriptome is highly cell-line specific.

Keywords
Sda antigen cancer stem cells non-adherent growth sialyl Lewis antigens transcriptomic analysis
MeSH Terms
Cell Line Cell Line, Tumor Colonic Neoplasms/genetics,metabolism Fucosyltransferases/genetics,metabolism Glycosyltransferases/metabolism Humans Lewis X Antigen/metabolism N-Acetylgalactosaminyltransferases/genetics,metabolism Neoplastic Stem Cells/metabolism,physiology Oligosaccharides/genetics,immunology,metabolism Sialyl Lewis X Antigen/metabolism,physiology Transfection Tumor Cells, Cultured
Chemicals
Lewis X Antigen Oligosaccharides Sd(a) determinant Sialyl Lewis X Antigen Glycosyltransferases Fucosyltransferases N-Acetylgalactosaminyltransferases beta-1,4-N-acetyl-galactosaminyl transferase 2 FUT6 protein, human
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Pucci Michela
Department of Experimental, Diagnostic and Specialty Medicine (DIMES), General Pathology Building, University of Bologna, Via San Giacomo 14, 40126 Bologna, Italy.
Gomes Ferreira Inês
Department of Experimental, Diagnostic and Specialty Medicine (DIMES), General Pathology Building, University of Bologna, Via San Giacomo 14, 40126 Bologna, Italy.
Malagolini Nadia
Department of Experimental, Diagnostic and Specialty Medicine (DIMES), General Pathology Building, University of Bologna, Via San Giacomo 14, 40126 Bologna, Italy.
Ferracin Manuela ORCID
Department of Experimental, Diagnostic and Specialty Medicine (DIMES), General Pathology Building, University of Bologna, Via San Giacomo 14, 40126 Bologna, Italy.
Dall'Olio Fabio ORCID
Department of Experimental, Diagnostic and Specialty Medicine (DIMES), General Pathology Building, University of Bologna, Via San Giacomo 14, 40126 Bologna, Italy.
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Article Info
Journal
International journal of molecular sciences
Abbr.
Int J Mol Sci
ISSN
1422-0067
DOI
10.3390/ijms21186558
Published
2020-09-08
Epub
2020-00-08
Language
English
Region
Switzerland
NLM ID
101092791
PMCID
PMC7555213
Subset
IM
Grants
Horizon 2020 · 676421
External Links
PubMed source DOI: 10.3390/ijms21186558 PMC Full Text View journal details
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