Tissue-specificity of heparan sulfate biosynthetic machinery in cancer

摘要: Heparan sulfate (HS) proteoglycans are key components of cell microenvironment and fine structure their polysaccharide HS chains plays an important role in cell-cell interactions, adhesion, migration signaling. It is formed on non-template basis, so, functional activity biosynthetic machinery crucial for correct biosynthesis post-synthetic modification. To reveal cancer-related changes transcriptional pattern system, the expression metabolism-involved genes (EXT1/2, NDST1/2, GLCE, 3OST1/HS3ST1, SULF1/2, HPSE) human normal (fibroblasts, PNT2) cancer (MCF7, LNCaP, PC3, DU145, H157, H647, A549, U2020, U87, HT116, KRC/Y) lines breast, prostate, colon tumors was studied. Real-time RT-PCR Western-blot analyses revealed specific patterns levels system both different vitro cancers vivo. Balance between activities elongation- modification- involved suggested as most informative parameter characterization. Normal fibroblasts showed elongation-oriented biosynthesis, while PNT2 prostate epithelial cells had modification-oriented one. However, demonstrated common tendency to acquire fibroblast-like mode system. Surprisingly, aggressive metastatic (U2020, retained similar cells, possibly enabling keep like-to-normal surface glycosylation escape antimetastatic control. The obtained results show type-specific HS-biosynthetic tissue-specific vivo, supporting a close involvement carcinogenesis.