2nd Department of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Greece.
J Eur Acad Dermatol Venereol. 2011 Jun;25(6):679-87. doi: 10.1111/j.1468-3083.2010.03851.x. Epub 2010 Sep 16.
Basal cell carcinoma (BCC) is one of the most frequent forms of malignancy in humans. Although BCC is a tumour of low degree of malignancy, if left untreated, it can be locally aggressive, eat away at tissues and cause ulceration. Nodular is the most common subtype of BCC (>50%). Although apparently non-invasive, micronodular, a certain subgroup of nodular, is likely to recur. Glycosaminoglycans (GAGs), such as hyaluronic acid (HA), are extracellular matrix molecules of high importance in malignant transformation, metastasis and other complex remodelling processes.
To investigate the expression of GAGs and their metabolizing enzymes in nodular BCC, when compared with adjacent healthy human skin tissue specimens.
Total GAGs were isolated and purified from nodular BCC and normal adjacent human skin tissue specimens. GAGs were subsequently fractionated by electrophoresis on cellulose acetate membranes and characterized using specific GAG-degrading enzymes. The content of HA in total GAGs was measured using ELISA and the expression of HA synthases (HAS), hyaluronidases (HYAL) and HA receptors (CD44 and receptor hyaluronic acid-mediated motility (RHAMM) was assessed using RT-PCR.
Nodular BCC is associated with increased levels of HA concomitant with upregulation of gene expression of HAS3, HYAL3 and RHAMM, when compared with normal adjacent skin.
These results indicate that HA homeostasis in nodular BCC shows distinct features which may be helpful in understanding the complex behaviour of nodular subtype of BCC, thus eventually leading to new treatment strategies.
基底细胞癌(BCC)是人类最常见的恶性肿瘤之一。尽管 BCC 是一种低度恶性肿瘤,如果不治疗,它可能具有局部侵袭性,侵蚀组织并导致溃疡。结节型是最常见的 BCC 亚型(>50%)。尽管微结节型似乎是非侵袭性的,但它是结节型的一个亚组,可能会复发。糖胺聚糖(GAGs),如透明质酸(HA),是恶性转化、转移和其他复杂重塑过程中非常重要的细胞外基质分子。
研究与相邻健康人皮肤组织标本相比,GAGs 及其代谢酶在结节型 BCC 中的表达情况。
从结节型 BCC 和正常相邻人皮肤组织标本中分离和纯化总 GAGs。随后,将 GAGs 进行醋酸纤维素膜电泳分离,并使用特异性 GAG 降解酶进行鉴定。使用 ELISA 测量总 GAG 中 HA 的含量,并使用 RT-PCR 评估 HA 合成酶(HAS)、透明质酸酶(HYAL)和 HA 受体(CD44 和受体透明质酸介导的运动(RHAMM)的表达。
与正常相邻皮肤相比,结节型 BCC 与 HA 水平升高相关,同时 HAS3、HYAL3 和 RHAMM 的基因表达上调。
这些结果表明,结节型 BCC 中的 HA 动态平衡具有独特的特征,这有助于理解结节型 BCC 的复杂行为,从而最终导致新的治疗策略。