Mannello Ferdinando, Maccari Francesca, Ligi Daniela, Santi Martina, Gatto Francesco, Linhardt Robert J, Galeotti Fabio, Volpi Nicola
Department of Biomolecular Sciences, Section of Clinical Biochemistry, Unit of Cell Biology, University "Carlo Bo", Urbino, 61029, Italy.
Cell Biochem Funct. 2015 Apr;33(3):128-33. doi: 10.1002/cbf.3096. Epub 2015 Mar 6.
Breast cyst fluid (BCF) contained in gross cists is involved with its many biomolecules in different stages of breast cystic development. Type I apocrine and type II flattened cysts are classified based on biochemical, morphological and hormonal differences, and their different patterns of growth factors and active biocompounds may require different regulation. In a previous paper, hyaluronic acid in a very low content and chondroitin sulphate/dermatan sulphate were identified and characterized in BCF. In this new study, various apocrine and flattened BCFs were analyzed for HS concentration and disaccharide pattern. Apocrine HS was found specifically constituted of N-acetyl groups contrary to flattened HS richer in N-sulphate disaccharides with an overall N-acetylated/N-sulphated ratio significantly increased in apocrine compared with flattened (13.5 vs 3.7). Related to this different structural features, the charge density significantly decreased (-30%) in apocrine versus flattened BCFs. Finally, no significant differences were observed for HS amount (0.9-1.3 µg ml(-1) ) between the two BCF types even if a greater content was determined for flattened samples. The specifically N-sulphated sequences in flattened BCF HS can exert biologic capacity by regulating growth factors activity. On the other hand, we cannot exclude a peculiar regulation of the activity of biomolecules in apocrine BCF by HS richer in N-acetylated disaccharides. In fact, the different patterns of growth factors and active biocompounds in the two types of cysts may require different regulation by specific sequences in the HS backbone possessing specific structural characteristics and distinctive chemical groups.
大体囊肿中所含的乳腺囊肿液(BCF)在乳腺囊肿发育的不同阶段涉及其众多生物分子。根据生化、形态和激素差异,将I型大汗腺囊肿和II型扁平囊肿进行分类,它们不同的生长因子和活性生物化合物模式可能需要不同的调节。在之前的一篇论文中,已在BCF中鉴定并表征了极低含量的透明质酸以及硫酸软骨素/硫酸皮肤素。在这项新研究中,分析了各种大汗腺和扁平BCF的硫酸乙酰肝素(HS)浓度和二糖模式。发现大汗腺HS特别由N - 乙酰基组成,这与富含N - 硫酸二糖的扁平HS相反,与扁平型相比,大汗腺型的总体N - 乙酰化/N - 硫酸化比率显著增加(13.5对3.7)。与这种不同的结构特征相关,大汗腺型与扁平型BCF相比,电荷密度显著降低(约 - 30%)。最后,即使确定扁平样品中的含量更高,但两种BCF类型之间的HS量(约0.9 - 1.3μg/ml)未观察到显著差异。扁平BCF HS中特定的N - 硫酸化序列可通过调节生长因子活性发挥生物学功能。另一方面,我们不能排除富含N - 乙酰化二糖的HS对大汗腺BCF中生物分子活性的特殊调节作用。事实上,两种类型囊肿中生长因子和活性生物化合物的不同模式可能需要具有特定结构特征和独特化学基团的HS主链中的特定序列进行不同的调节。