Mukunyadzi Perkins, Liu Kela, Hanna Ehab Y, Suen James Y, Fan Chun-Yang
Department of Pathology, University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System, Little Rock, Arkansas 72205, USA.
Mod Pathol. 2003 Aug;16(8):796-801. doi: 10.1097/01.MP.0000081731.17549.53.
Syndecan-1 (CD138), a cell-surface heparan sulfate proteoglycan, is involved in cell-cell, cell-matrix interaction and growth factor binding. Loss of expression of syndecan-1 in tumor cells leads to decreased intercellular cohesion, increased potential for tumor invasiveness, and metastatic spread. Furthermore, induction of syndecan-1 expression in the tumor stroma has been postulated to promote tumor angiogenesis via its binding to growth factors such as basic fibroblast growth factor. Although syndecan-1 expression within tumor cells has been investigated in head and neck squamous cell carcinoma, stromal expression has not been studied in detail. We analyzed 38 cases of head and neck squamous cell carcinoma by immunohistochemical staining for syndecan-1 expression within the stroma. The expression of syndecan-1 within tumor cells of various histologic grades of differentiation, squamous cell carcinoma in situ cells, and benign squamous epithelium was also determined. Variable levels of diminished syndecan-1 expression were noted within the dysplastic cells of 9 of 16 (60%) squamous cell carcinoma in situ lesions and in all 38 (100%) invasive squamous cell carcinoma. In general, higher levels of syndecan-1 expression were observed in the well-differentiated tumors, in contrast to significant reduction of expression seen in poorly differentiated tumors. Syndecan-1 expression was observed within the stroma (in fibroblasts) surrounding infiltrating carcinoma cells in 28 of 38 (74%) cases. The intensity of syndecan-1 staining within the stroma showed generally an inverse correlation with the degree of tumor cell differentiation. Syndecan-1 expression was not detected in the stroma beneath normal squamous epithelium or adjacent to areas of squamous cell carcinoma in situ. We conclude that induced expression of syndecan-1 in the stroma surrounding tumor cells of invasive head and neck squamous cell carcinoma is a frequent event. The increased stromal syndecan-1 expression, coupled with its loss from the surface of carcinoma cells, may contribute to tumor cell invasion and the development of metastases.
Syndecan-1(CD138)是一种细胞表面硫酸乙酰肝素蛋白聚糖,参与细胞间、细胞与基质的相互作用以及生长因子结合。肿瘤细胞中Syndecan-1表达缺失会导致细胞间黏附力下降、肿瘤侵袭和转移扩散的可能性增加。此外,有人推测肿瘤基质中Syndecan-1表达的诱导通过其与碱性成纤维细胞生长因子等生长因子的结合来促进肿瘤血管生成。尽管在头颈部鳞状细胞癌中已对肿瘤细胞内的Syndecan-1表达进行了研究,但基质表达尚未得到详细研究。我们通过免疫组织化学染色分析了38例头颈部鳞状细胞癌基质中Syndecan-1的表达情况。还测定了不同组织学分化等级的肿瘤细胞、原位鳞状细胞癌细胞和良性鳞状上皮中Syndecan-1的表达。在16例原位鳞状细胞癌病变中的9例(60%)发育异常细胞以及所有38例(100%)浸润性鳞状细胞癌中,均观察到Syndecan-1表达水平不同程度降低。一般来说,在高分化肿瘤中观察到较高水平的Syndecan-1表达,与之形成对比的是,在低分化肿瘤中表达明显降低。在38例(74%)病例中,浸润性癌细胞周围的基质(成纤维细胞中)观察到Syndecan-1表达。基质中Syndecan-1染色强度通常与肿瘤细胞分化程度呈负相关。在正常鳞状上皮下方或原位鳞状细胞癌区域附近的基质中未检测到Syndecan-1表达。我们得出结论,侵袭性头颈部鳞状细胞癌肿瘤细胞周围基质中Syndecan-1的诱导表达是常见现象。基质中Syndecan-1表达增加,再加上其从癌细胞表面缺失,可能有助于肿瘤细胞侵袭和转移的发生。