MMP-10 (Stromelysin-2) and MMP-21 in human and murine squamous cell cancer

MMP-10 (Stromelysin-2) and MMP-21 in human and murine squamous cell cancer
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DOI:
10.1111/j.1600-0625.2009.00901.x
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发表时间:
2009-12-01
影响因子:
3.6
通讯作者:
Saarialho-Kere, Ulpu
Saarialho-Kere, Ulpu
中科院分区:
医学2区
文献类型:
--
作者:
Boyd, Sonja;Virolainen, Susanna;Saarialho-Kere, Ulpu

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肾移植受者的鳞状细胞癌(SCC)比非免疫功能低下人群更具有侵袭性,转移更早。基质金属蛋白酶(matrix metalloproteinases,MMPs)在肿瘤的发生、侵袭和转移中起重要作用。我们的目的是比较MMPs-10、-12和-21在来自免疫抑制(IS)和对照患者的SCC中的表达,以及MMPs-10和-21对FVB/N-Tg(KRT 5-Nfkbia)3Rto小鼠系中SCC发展的贡献。对25对匹配的SCC、9例Bowen病和选择性抑制Rel/NF-κ B信号传导的小鼠的定时背部皮肤活检进行免疫组织化学分析。半定量评估基质MMP-10的表达较高(P = 0.009),在对照组相比,IS患者。肿瘤细胞来源的MMP-10、MMP-12和MMP-21的表达在各组之间没有差异,但对照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表达,而MMP-21不存在。MMP-10和-21存在于衰老小鼠的炎症或基质细胞中,而不典型增生的角质形成细胞和浸润性癌为阴性。我们的研究结果表明,MMP-10可能是重要的SCC进展的初始阶段,并在基质中诱导有关的一般主机反应皮肤癌。MMP-21与SCC的侵袭无关,但可能参与角质形成细胞的分化。
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-kappa B 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.