Li Y, Heldin P
Department of Medical Biochemistry and Microbiology, Biomedical Center, Uppsala University, Box 575S-751 23 Uppsala, Sweden.
Br J Cancer. 2001 Aug 17;85(4):600-7. doi: 10.1054/bjoc.2001.1922.
Malignant pleural mesotheliomas is in most cases associated with elevated amounts of hyaluronan. To investigate the importance of hyaluronan for the malignant properties of mesotheliomas, we have expressed murine hyaluronan synthase 2 (HAS2) in the non-hyaluronan producing mesothelioma cell line, Mero-25. We found that upon hyaluronan overproduction the mesothelioma cells changed their epitheloid character to a fibroblastic phenotype and were surrounded by pericellular matrices, the size of which correlated to the amount of synthesized hyaluronan. HAS2-transfected cells with the ability to synthesize about 520 ng hyaluronan/5 x 10(4)cells/24 h exhibited about a 2-fold increase in the expression of the cell surface hyaluronan receptor CD44 and their locomotion increased compared to that of mock-transfected Mero-25 cells. Furthermore, the malignant properties of mesothelioma cell clones as determined by the ability to grow in a soft agar assay correlated to their hyaluronan production. These results provide evidence for an important role of hyaluronan in the aggressive spread of mesotheliomas in adjacent non-cancerous stromal tissues.
大多数情况下，恶性胸膜间皮瘤与透明质酸含量升高有关。为了研究透明质酸对间皮瘤恶性特性的重要性，我们在不产生透明质酸的间皮瘤细胞系Mero-25中表达了小鼠透明质酸合酶2（HAS2）。我们发现，当透明质酸过量产生时，间皮瘤细胞将其上皮样特征转变为成纤维细胞表型，并被细胞周基质包围，其大小与合成的透明质酸量相关。能够合成约520 ng透明质酸/5×10⁴个细胞/24小时的HAS2转染细胞，其细胞表面透明质酸受体CD44的表达增加了约2倍，并且与空载体转染的Mero-25细胞相比，其运动能力增强。此外，通过软琼脂试验测定的间皮瘤细胞克隆的恶性特性与其透明质酸产生相关。这些结果为透明质酸在间皮瘤向相邻非癌性基质组织的侵袭性扩散中起重要作用提供了证据。
