Human matrix metalloproteinase-21 (MMP-21), the newest member of the MMP gene family, has been suggested to play an important role in embryogenesis and tumor progression and to be a target of the Wnt, Pax, and Notch signaling pathways. Here we report detection of MMP-21 by RT-PCR in mouse embryos aged 10.5, 12.5, 13.5, and 16.5 days, as well as in various adult murine organs. In both humans and mice, MMP-21 protein was detected in the epithelial cells of developing kidney, intestine, neuroectoderm, and skin but not in normal adult skin using immunohistochemistry with two unrelated antibodies. However, it was present in invasive cancer cells of aggressive subtypes of basal and squamous cell carcinomas, although it was not expressed in skin disorders characterized by mere keratinocyte hyperproliferation. Of several cytokines tested, transforming growth factor-beta1 induced MMP-21 in vitro in HaCaTs and keratinocytes as judged by real-time quantitative TaqMan PCR. Although suprabasal differentiating keratinocytes expressed MMP-21 in developing skin in vivo, MMP-21-positive keratinocytes were detected by immunohistochemistry in both low and high calcium cultures. MMP-21 expression was not up-regulated by ras transformation in HaCaT cell lines (HaCaT, A5, II-4, and RT3); in skin and colon cancers, its expression did not associate with apoptosis, beta-catenin transactivation, or epithelial MMPs-9 and -10. However, MMP-21 protein was found in the same regions as MMP-7 but not in the same cells. Our results suggest that during development, MMP-21 expression is temporally and spatially tightly controlled. Unlike many classical MMPs, it is present in various normal adult tissues. Among epithelial MMPs, MMP-21 has a unique expression pattern in cancer.

中文翻译：

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Matrix metalloproteinase-21 在发育过程中和癌症中在上皮细胞中表达，并通过角质形成细胞中的转化生长因子-β1 上调。

人基质金属蛋白酶 21 (MMP-21) 是 MMP 基因家族的最新成员，已被认为在胚胎发生和肿瘤进展中发挥重要作用，并且是 Wnt、Pax 和 Notch 信号通路的靶标。在这里，我们报告了通过 RT-PCR 在 10.5、12.5、13.5 和 16.5 天的小鼠胚胎以及各种成年小鼠器官中检测到 MMP-21。在人类和小鼠中，使用两种不相关抗体的免疫组织化学方法，在发育中的肾脏、肠道、神经外胚层和皮肤的上皮细胞中检测到 MMP-21 蛋白，但在正常成人皮肤中未检测到。然而，它存在于基底细胞癌和鳞状细胞癌侵袭性亚型的侵袭性癌细胞中，尽管它在仅以角质形成细胞过度增殖为特征的皮肤病中不表达。在测试的几种细胞因子中，通过实时定量 TaqMan PCR 判断，转化生长因子-β1 在 HaCaT 和角质形成细胞中体外诱导 MMP-21。尽管基底上分化角质形成细胞在体内发育中的皮肤中表达 MMP-21，但在低钙和高钙培养物中均通过免疫组织化学检测到 MMP-21 阳性角质形成细胞。在 HaCaT 细胞系（HaCaT、A5、II-4 和 RT3）中，ras 转化不会上调 MMP-21 表达；在皮肤癌和结肠癌中，其表达与细胞凋亡、β-连环蛋白反式激活或上皮 MMPs-9 和 -10 无关。然而，MMP-21 蛋白与 MMP-7 存在于相同的区域，但不存在于相同的细胞中。我们的结果表明，在发育过程中，MMP-21 表达在时间和空间上受到严格控制。与许多经典的 MMP 不同，它存在于各种正常的成人组织中。