Proteoglycans as potential microenvironmental biomarkers for colon cancer

Abstract

Glycosylation changes occur widely in colon tumours, suggesting glycosylated molecules as potential biomarkers for colon cancer diagnostics. In this study, proteoglycans (PGs) expression levels and their transcriptional patterns are investigated in human colon tumours in vivo and carcinoma cells in vitro. According to RT-PCR analysis, normal and cancer colon tissues expressed a specific set of PGs (syndecan-1, perlecan, decorin, biglycan, versican, NG2/CSPG4, serglycin, lumican, CD44), while the expression of glypican-1, brevican and aggrecan was almost undetectable. Overall transcriptional activity of the PGs in normal and cancer tissues was similar, although expression patterns were different. Expression of decorin and perlecan was down-regulated 2-fold in colon tumours, while biglycan and versican expression was significantly up-regulated (6-fold and 3-fold, respectively). Expression of collagen1A1 was also increased 6-fold in colon tumours. However, conventional HCT-116 colon carcinoma and AG2 colon cancer-initiating cells did not express biglycan and decorin and were versican-positive and -negative, respectively, demonstrating an extracellular origin of the PGs in cancer tissue. Selective expression of heparan sulfate (HS) proteoglycans syndecan-1 and perlecan in the AG2 colon cancer-initiating cell line suggests these PGs as potential biomarkers for cancer stem cells. Overall transcriptional activity of the HS biosynthetic system was similar in normal and cancer tissues, although significant up-regulation of extracellular sulfatases SULF1/2 argues for a possible distortion of HS sulfation patterns in colon tumours. Taken together, the obtained results suggest versican, biglycan, collagen1A1 and SULF1/2 expression as potential microenvironmental biomarkers and/or targets for colon cancer diagnostics and treatment.

Syndecan-1 is a novel molecular marker for triple negative inflammatory breast cancer and modulates the cancer stem cell phenotype via the IL-6/STAT3, Notch and EGFR signaling pathways

“…Of note, Syndecan-1 expression is enriched in CD44 + subpopulation in SUM-149 cells, although this enrichment is less in SKBR3 cells. This is in agreement with the notion of interaction between Syndecan-1 and CD44 promoting glioma cell invasion [56] and suggesting a physical and functional association as previously described [57, 58]. …”

Tissue-specificity of heparan sulfate biosynthetic machinery in cancer

“…Complex analysis of transcriptional activity of HS biosynthetic system in normal prostate tissue and tumors showed significant downregulation of total transcriptional activity of HS biosynthetic system and changes in overall expression patterns in prostate cancer, 33 whereas in colon cancer only qualitative changes in expression patterns are detected. 34 All the results suggest direct involvement of HS biosynthetic machinery in carcinogenesis and show complex changes of HS metabolic enzymes expression in tumors. However, the matter remains still poorly investigated.…”

Extracellular Matrix, a Hard Player in Angiogenesis

“…Heparan sulfate PG (HSPG) such as syndecans and glypicans are regulators of cancer progression and angiogenesis and serve as biomarkers for early detection and/or as pharmacological targets [116,117,118]. Notably, high concentrations of condroitin sulfate PG (CSPG), in particular versican and decorin, have been reported in the tumor stroma [111,119,120]. The major PGs affecting tumor angiogenesis are described below.…”