Background: The expression of a specific set of genes controls the different structures of heparan sulfate\r\nproteoglycans (HSPGs), which are involved in the growth, invasion and metastatic properties of cancerous cells. The\r\npurpose of this study is to increase knowledge of HSPG alterations in breast cancer.\r\nMethods: Twenty-three infiltrating ductal adenocarcinomas (IDCs), both metastatic and non-metastatic were\r\nstudied. A transcriptomic approach to the structure of heparan sulfate (HS) chains was used, employing qPCR to\r\nanalyze both the expression of the enzymes involved in their biosynthesis and editing, as well as the proteoglycan\r\ncore proteins. Since some of these proteoglycans can also carry chondroitin sulfate chains, we extended the study\r\nto include the genes involved in the biosynthesis of these glycosaminoglycans. Histochemical techniques were also\r\nused to analyze tissular expression of particular genes showing significant expression differences, of potential\r\ninterest.\r\nResults: No significant change in transcription was detected in approximately 70% of analyzed genes. However, 13\r\ndemonstrated changes in both tumor types (40% showing more intense deregulation in the metastatic), while 5\r\ngenes showed changes only in non-metastatic tumors. Changes were related to 3 core proteins: overexpression of\r\nsyndecan-1 and underexpression of glypican-3 and perlecan. HS synthesis was affected by lower levels of some\r\n3-O-sulfotransferase transcripts, the expression of NDST4 and, only in non metastatic tumors, higher levels of\r\nextracellular sulfatases. Furthermore, the expression of chondroitin sulfate also was considerably affected, involving\r\nboth the synthesis of the saccharidic chains and sulfations at all locations. However, the pro-metastatic enzyme\r\nheparanase did not exhibit significant changes in mRNA expression, although in metastatic tumors it appeared\r\nrelated to increased levels of the most stable form of mRNA. Finally, the expression of heparanase 2, which displays\r\nanti-metastatic features, experienced a strong deregulation in all patients analyzed.\r\nConclusions: IDCs show alterations in the expression of HSPG genes; principally the expression and localization of\r\nproteoglycans and the sulfation patterns of glycosaminoglycan chains, depending on the metastatic nature of the\r\ntumor. In addition, the anti-proliferative molecule heparanase 2 experiences strong deregulation, thus highlighting\r\nit as a potentially interesting diagnostic factor.
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