Heparan sulfate proteoglycans undergo differential expression alterations in right sided colorectal cancer, depending on their metastatic characterReportar como inadecuado




Heparan sulfate proteoglycans undergo differential expression alterations in right sided colorectal cancer, depending on their metastatic character - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

BMC Cancer

, 15:742

First Online: 20 October 2015Received: 13 March 2015Accepted: 08 October 2015DOI: 10.1186-s12885-015-1724-9

Cite this article as: Fernández-Vega, I., García-Suárez, O., García, B. et al. BMC Cancer 2015 15: 742. doi:10.1186-s12885-015-1724-9

Abstract

BackgroundHeparan sulfate proteoglycans HSPGs are complex molecules involved in the growth, invasion and metastatic properties of cancerous cells. This study analyses the alterations in the expression patterns of these molecules in right sided colorectal cancer CRC, both metastatic and non-metastatic.

MethodsTwenty right sided CRCs were studied. A transcriptomic approach was used, employing qPCR to analyze both the expression of the enzymes involved in heparan sulfate HS chains biosynthesis, as well as the proteoglycan core proteins. Since some of these proteoglycans can also carry chondroitin sulfate CS chains, we include the study of the genes involved in the biosynthesis of these glycosaminoglycans. Immunohistochemical techniques were also used to analyze tissue expression of particular genes showing significant expression differences, of potential interest.

ResultsChanges in proteoglycan core proteins differ depending on their location; those located intracellularly or in the extracellular matrix show very similar alteration patterns, while those located on the cell surface vary greatly depending on the nature of the tumor: glypicans 1, 3, 6 and betaglycan are affected in the non-metastatic tumors, whereas in the metastatic, only glypican-1 and syndecan-1 are modified, the latter showing opposing alterations in levels of RNA and of protein, suggesting post-transcriptional regulation in these tumors. Furthermore, in non-metastatic tumors, polymerization of glycosaminoglycan chains is modified, particularly affecting the synthesis of the tetrasaccharide linker and the initiation and elongation of CS chains, HS chains being less affected. Regarding the enzymes responsible for the modificaton of the HS chains, alterations were only found in non-metastatic tumors, affecting N-sulfation and the isoforms HS6ST1, HS3ST3B and HS3ST5. In contrast, synthesis of the CS chains suggests changes in epimerization and sulfation of the C4 and C2 in both types of tumor.

ConclusionsRight sided CRCs show alterations in the expression of HSPGs, including the expression of the cell surface core proteins, many glycosiltransferases and some enzymes that modify the HS chains depending on the metastatic nature of the tumor, resulting more affected in non-metastatic ones. However, matrix proteoglycans and enzymes involved in CS fine structure synthesis are extensively modified independetly of the presence of lymph node metastasis.

KeywordsColorectal cancer Heparan sulfate Proteoglycan Glycosaminoglycan Chondroitin sulfate AbbreviationsCRCColorectal cancer

CSChondroitin sulfate

DSDermatan sulfate

ECMExtracellular matrix

GAGGlycosaminoglycan

GalNAcN-acetyl-D-galactosamine

GlcAD-glucuronic acid

GlcNAcN-acetyl-D-glucosamine

GTGlycosyltransferase

HSHeparan sulfate

HSPGHeparan sulfate proteoglycan

IdoAIduronate

Electronic supplementary materialThe online version of this article doi:10.1186-s12885-015-1724-9 contains supplementary material, which is available to authorized users.

Download fulltext PDF



Autor: Iván Fernández-Vega - Olivia García-Suárez - Beatriz García - Ainara Crespo - Aurora Astudillo - Luis M. Quirós

Fuente: https://link.springer.com/







Documentos relacionados