Heparan sulfate proteoglycans undergo differential expression alterations in left sided colorectal cancer, depending on their metastatic character
Abstract Background Heparan sulfate proteoglycans (HSPGs) are complex molecules which play a role in the invasion and growth and metastatic properties of cancerous cells. In this work we analyze changes in the patterns of expression of HSPGs in left sided colorectal cancer (LSCRC), both metastatic a...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-06-01
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| Series: | BMC Cancer |
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| Online Access: | http://link.springer.com/article/10.1186/s12885-018-4597-x |
| _version_ | 1811310203701821440 |
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| author | Ainara Crespo Olivia García-Suárez Iván Fernández-Vega María Pilar Solis-Hernandez Beatriz García Sonia Castañón Luis M. Quirós |
| author_facet | Ainara Crespo Olivia García-Suárez Iván Fernández-Vega María Pilar Solis-Hernandez Beatriz García Sonia Castañón Luis M. Quirós |
| author_sort | Ainara Crespo |
| collection | DOAJ |
| description | Abstract Background Heparan sulfate proteoglycans (HSPGs) are complex molecules which play a role in the invasion and growth and metastatic properties of cancerous cells. In this work we analyze changes in the patterns of expression of HSPGs in left sided colorectal cancer (LSCRC), both metastatic and non-metastatic, and the results are also compared with those previously obtained for right sided tumors (RSCRCs). Methods Eighteen LSCRCs were studied using qPCR to analyze the expression of both the proteoglycan core proteins and the enzymes involved in heparan sulfate chain biosynthesis. Certain HSPGs also carry chondroitin sulfate chains and so we also studied the genes involved in its biosynthesis. The expression of certain genes that showed significant expression differences were also analysed using immunohistochemical techniques. Results Changes in proteoglycan core proteins were dependent on their location, and the main differences between metastatic and non-metastatic tumors affected cell-surface glypicans, while other molecules were quite similar. Glypicans were also responsible for the main differences between RS- and LS- malignances. Regarding the biosynthesis of heparan sulfate chains, differential alterations in transcription depending on the presence or not of metastasis affected genes involved in the modification of uronic acid (epimerization and 2-O sulfation), and some isoforms responsible for sulfation of glucosamine (NDST1, HS6ST1). Moreover, in RSCRCs differences were preferentially found in the expression of genes involved in C6 and C3 sulfation of glucosamine, but not in NDSTs or SULFs. Finally, synthesis of chondroitin sulfate showed some alterations, which affected various steps, including polimerization and the modification of chains, but the main variations dependent on the presence of metastases were epimerization and 6C sulfation; however, when compared with RSCRCs, the essential divergences affected polymerization of the chains and the 6C sulfation of the galactosamine residue. Conclusions We evidenced alterations in the expression of HSPGs, including the expression of cell surface core proteins, many glycosiltransferases and some enzymes that modify the GAG chains in LSCRCs, but this was dependent on the metastatic nature of the tumor. Some of these alterations are shared with RSCRCs, while others, focused on specific gene groups, are dependent on tumor localization. |
| first_indexed | 2024-04-13T09:54:10Z |
| format | Article |
| id | doaj.art-eab9d9846d6349beb577314b706089bf |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-13T09:54:10Z |
| publishDate | 2018-06-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-eab9d9846d6349beb577314b706089bf2022-12-22T02:51:29ZengBMCBMC Cancer1471-24072018-06-0118111710.1186/s12885-018-4597-xHeparan sulfate proteoglycans undergo differential expression alterations in left sided colorectal cancer, depending on their metastatic characterAinara Crespo0Olivia García-Suárez1Iván Fernández-Vega2María Pilar Solis-Hernandez3Beatriz García4Sonia Castañón5Luis M. Quirós6Department of Biotechnology, Neiker-Tecnalia ArkauteInstituto Universitario Fernández-Vega, and Department of Morphology and Cell Biology, University of OviedoInstituto Universitario Fernández-Vega, and Department of Pathology, Hospital Universitario Central de AsturiasDepartment of Medical Oncology, Hospital Universitario Central de AsturiasInstituto Universitario Fernández-Vega, and Department of Functional Biology, University of OviedoDepartment of Biotechnology, Neiker-Tecnalia ArkauteInstituto Universitario Fernández-Vega, and Department of Functional Biology, University of OviedoAbstract Background Heparan sulfate proteoglycans (HSPGs) are complex molecules which play a role in the invasion and growth and metastatic properties of cancerous cells. In this work we analyze changes in the patterns of expression of HSPGs in left sided colorectal cancer (LSCRC), both metastatic and non-metastatic, and the results are also compared with those previously obtained for right sided tumors (RSCRCs). Methods Eighteen LSCRCs were studied using qPCR to analyze the expression of both the proteoglycan core proteins and the enzymes involved in heparan sulfate chain biosynthesis. Certain HSPGs also carry chondroitin sulfate chains and so we also studied the genes involved in its biosynthesis. The expression of certain genes that showed significant expression differences were also analysed using immunohistochemical techniques. Results Changes in proteoglycan core proteins were dependent on their location, and the main differences between metastatic and non-metastatic tumors affected cell-surface glypicans, while other molecules were quite similar. Glypicans were also responsible for the main differences between RS- and LS- malignances. Regarding the biosynthesis of heparan sulfate chains, differential alterations in transcription depending on the presence or not of metastasis affected genes involved in the modification of uronic acid (epimerization and 2-O sulfation), and some isoforms responsible for sulfation of glucosamine (NDST1, HS6ST1). Moreover, in RSCRCs differences were preferentially found in the expression of genes involved in C6 and C3 sulfation of glucosamine, but not in NDSTs or SULFs. Finally, synthesis of chondroitin sulfate showed some alterations, which affected various steps, including polimerization and the modification of chains, but the main variations dependent on the presence of metastases were epimerization and 6C sulfation; however, when compared with RSCRCs, the essential divergences affected polymerization of the chains and the 6C sulfation of the galactosamine residue. Conclusions We evidenced alterations in the expression of HSPGs, including the expression of cell surface core proteins, many glycosiltransferases and some enzymes that modify the GAG chains in LSCRCs, but this was dependent on the metastatic nature of the tumor. Some of these alterations are shared with RSCRCs, while others, focused on specific gene groups, are dependent on tumor localization.http://link.springer.com/article/10.1186/s12885-018-4597-xColorectal cancerHeparan sulfateProteoglycanGlycosaminoglycanChondroitin sulfate |
| spellingShingle | Ainara Crespo Olivia García-Suárez Iván Fernández-Vega María Pilar Solis-Hernandez Beatriz García Sonia Castañón Luis M. Quirós Heparan sulfate proteoglycans undergo differential expression alterations in left sided colorectal cancer, depending on their metastatic character BMC Cancer Colorectal cancer Heparan sulfate Proteoglycan Glycosaminoglycan Chondroitin sulfate |
| title | Heparan sulfate proteoglycans undergo differential expression alterations in left sided colorectal cancer, depending on their metastatic character |
| title_full | Heparan sulfate proteoglycans undergo differential expression alterations in left sided colorectal cancer, depending on their metastatic character |
| title_fullStr | Heparan sulfate proteoglycans undergo differential expression alterations in left sided colorectal cancer, depending on their metastatic character |
| title_full_unstemmed | Heparan sulfate proteoglycans undergo differential expression alterations in left sided colorectal cancer, depending on their metastatic character |
| title_short | Heparan sulfate proteoglycans undergo differential expression alterations in left sided colorectal cancer, depending on their metastatic character |
| title_sort | heparan sulfate proteoglycans undergo differential expression alterations in left sided colorectal cancer depending on their metastatic character |
| topic | Colorectal cancer Heparan sulfate Proteoglycan Glycosaminoglycan Chondroitin sulfate |
| url | http://link.springer.com/article/10.1186/s12885-018-4597-x |
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