Kerkelä E, Ala-Aho R, Jeskanen L, Rechardt O, Grénman R, Shapiro S D, Kähäri V M, Saarialho-Kere U
Department of Dermatology, Helsinki University Central Hospital, Finland.
J Invest Dermatol. 2000 Jun;114(6):1113-9. doi: 10.1046/j.1523-1747.2000.00993.x.
Matrix metalloproteinases play an essential role in tumor growth and invasion. Different matrix metalloproteinases are often expressed in cancers with distinct patterns. To investigate the role of human macrophage metalloelastase (MMP-12) in epidermal tumors, we studied human macrophage metalloelastase mRNA and protein expression in malignant squamous cell and basal cell carcinomas, and in premalignant Bowen's disease. Human macrophage metalloelastase was detected in 11 of 17 squamous cell carcinomas in epithelial cancer cells, whereas macrophages were positive in 15 of 17 samples. In basal cell carcinomas, human macrophage metalloelastase was more often found in macrophages (seven of 19) than in cancer cells (four of 19). Human macrophage metalloelastase mRNA was also detected in three cell lines derived from squamous cell carcinomas of the head and neck and in transformed HaCaT cells, whereas premalignant tumors and primary keratinocytes were negative for human macrophage metalloelastase mRNA. Western analysis revealed human macrophage metalloelastase protein in squamous cell carcinoma cells. Our results show that human macrophage metalloelastase can be expressed in vivo and in vitro by transformed epithelial cells and indicate that the level of human macrophage metalloelastase expression correlates with epithelial dedifferentiation and histologic aggressiveness.
基质金属蛋白酶在肿瘤生长和侵袭中起重要作用。不同的基质金属蛋白酶在癌症中常呈现不同的表达模式。为了研究人巨噬细胞金属弹性蛋白酶（MMP - 12）在表皮肿瘤中的作用，我们研究了人巨噬细胞金属弹性蛋白酶mRNA和蛋白在恶性鳞状细胞癌、基底细胞癌以及癌前鲍温病中的表达情况。在17例鳞状细胞癌的上皮癌细胞中有11例检测到了人巨噬细胞金属弹性蛋白酶，而在17个样本中有15例巨噬细胞呈阳性。在基底细胞癌中，人巨噬细胞金属弹性蛋白酶更多见于巨噬细胞（19例中有7例）而非癌细胞（19例中有4例）。在源自头颈部鳞状细胞癌的3种细胞系以及转化的HaCaT细胞中也检测到了人巨噬细胞金属弹性蛋白酶mRNA，而癌前肿瘤和原代角质形成细胞中人巨噬细胞金属弹性蛋白酶mRNA呈阴性。蛋白质印迹分析在鳞状细胞癌细胞中发现了人巨噬细胞金属弹性蛋白酶蛋白。我们的结果表明，人巨噬细胞金属弹性蛋白酶可在体内和体外由转化的上皮细胞表达，并且表明人巨噬细胞金属弹性蛋白酶的表达水平与上皮细胞去分化和组织学侵袭性相关。
