Department of Pathology, Helsinki University Central Hospital and Haartman Institute, University of Helsinki, Helsinki, Finland.
Exp Dermatol. 2009 Dec;18(12):1044-52. doi: 10.1111/j.1600-0625.2009.00901.x.
The squamous cell cancers (SCC) of renal transplant recipients are more aggressive and metastasize earlier than those of the non-immunocompromised population. Matrix metalloproteinases (MMPs) have a central role in tumor initiation, invasion and metastasis. Our aim was to compare the expression of MMPs-10, -12 and -21 in SCCs from immunosuppressed (IS) and control patients and the contribution of MMPs-10 and -21 to SCC development in the FVB/N-Tg(KRT5-Nfkbia)3Rto mouse line. Immunohistochemical analysis of 25 matched pairs of SCCs, nine of Bowen's disease and timed back skin biopsies of mice with selective inhibition of Rel/NF-kappaB signalling were performed. Semiquantitatively assessed stromal MMP-10 expression was higher (P = 0.009) in the control group when compared with IS patients. Tumor cell-derived MMP-10, -12 and -21 expression did not differ between the groups but stromal fibroblasts of the control SCCs tended to express MMP-21 more abundantly. MMP-10 expression was observed already in Bowen's disease while MMP-21 was absent. MMP-10 and -21 were present in inflammatory or stromal cells in ageing mice while dysplastic keratinocytes and invasive cancer were negative. Our results suggest that MMP-10 may be important in the initial stages of SCC progression and induced in the stroma relating to the general host-response reaction to skin cancer. MMP-21 does not associate with invasion of SCC but may be involved in keratinocyte differentiation.
肾移植受者的鳞状细胞癌（SCC）比非免疫抑制人群的更具侵袭性，转移更早。基质金属蛋白酶（MMPs）在肿瘤的发生、侵袭和转移中起着核心作用。我们的目的是比较免疫抑制（IS）和对照组患者 SCC 中 MMP-10、-12 和 -21 的表达，并研究 MMP-10 和 -21 对 FVB/N-Tg（KRT5-Nfkbia）3Rto 小鼠 SCC 发展的贡献。对 25 对 SCC、9 例 Bowen 病以及对选择性抑制 Rel/NF-κB 信号转导的小鼠背部皮肤进行了时间活检，进行了免疫组织化学分析。与 IS 患者相比，对照组 SCC 中基质 MMP-10 的表达更高（P=0.009）。肿瘤细胞来源的 MMP-10、-12 和 -21 的表达在两组之间没有差异，但对照组 SCC 的基质成纤维细胞倾向于更丰富地表达 MMP-21。在 Bowen 病中已经观察到 MMP-10 的表达，而 MMP-21 不存在。在衰老小鼠的炎症或基质细胞中存在 MMP-10 和 -21，而发育不良的角蛋白细胞和侵袭性癌症为阴性。我们的结果表明，MMP-10 可能在 SCC 进展的初始阶段很重要，并与皮肤癌的宿主反应有关。MMP-21 与 SCC 的侵袭无关，但可能参与角蛋白细胞分化。
