Stanley M J, Stanley M W, Sanderson R D, Zera R
Department of Surgery, Hennepin County Medical Center, Minneapolis, MN 55415, USA.
Am J Clin Pathol. 1999 Sep;112(3):377-83. doi: 10.1093/ajcp/112.3.377.
Loss of expression of the heparan sulfate proteoglycan syndecan-1 leads to reduced cell adhesion, increased invasive potential, and dysregulated growth of mammary epithelial cells in vitro. We compared syndecan-1 expression in malignant and nonmalignant breast tissues using immunohisto-chemistry with monoclonal antibody B-B4. Staining for syndecan-1 is greatly diminished on malignant cells within infiltrating ductal carcinomas (n = 20) as compared with ductal epithelium of both normal breast (n = 14) and stromal-epithelial neoplasms (n = 10), which exhibit extensive basolateral epithelial staining. Surprisingly, comparison of malignant and nonmalignant breast tissue also reveals a striking difference in expression of syndecan-1 within the stromal compartment. In infiltrating ductal carcinomas, strong staining for syndecan-1 is present both within the connective tissue and on stromal cell surfaces, whereas syndecan-1 expression is absent in the stroma of both normal breast and stromal-epithelial neoplasms. Because syndecan-1 interacts with heparin-binding growth factors such as FGF-2, accumulation of syndecan-1 within the tumor stroma may contribute to the extensive angiogenesis and stromal proliferation characteristic of infiltrating breast carcinoma. Moreover, the induction of syndecan-1 within the stroma, coupled with the loss of syndecan-1 on malignant cells, suggests that changes in syndecan-1 expression are critical in promoting the metastatic phenotype of infiltrating ductal carcinoma of the breast.
硫酸乙酰肝素蛋白聚糖syndecan-1表达缺失会导致体外乳腺上皮细胞的细胞黏附减少、侵袭潜能增加以及生长失调。我们使用单克隆抗体B-B4通过免疫组织化学方法比较了恶性和非恶性乳腺组织中syndecan-1的表达。与正常乳腺(n = 14)和基质-上皮肿瘤(n = 10)的导管上皮相比,浸润性导管癌(n = 20)内的恶性细胞上syndecan-1的染色明显减少,正常乳腺和基质-上皮肿瘤的导管上皮呈现广泛的基底外侧上皮染色。令人惊讶的是,恶性和非恶性乳腺组织的比较还显示出基质区室中syndecan-1表达的显著差异。在浸润性导管癌中,结缔组织内和基质细胞表面均存在syndecan-1的强染色,而正常乳腺和基质-上皮肿瘤的基质中均不存在syndecan-1表达。由于syndecan-1与肝素结合生长因子如FGF-2相互作用,肿瘤基质中syndecan-1的积累可能有助于浸润性乳腺癌特有的广泛血管生成和基质增殖。此外,基质中syndecan-1的诱导以及恶性细胞上syndecan-1的缺失表明,syndecan-1表达的变化对于促进乳腺浸润性导管癌的转移表型至关重要。