Song Jinna, Wang Jun, Yang Jianli, Jiang Chunhua, Shen Wei, Wang Li
Institute of Genetics and Cytology, School of Life Science, Northeast Normal University, Changchun, PR China.
Melanoma Res. 2006 Apr;16(2):119-26. doi: 10.1097/01.cmr.0000215029.62199.4c.
Angiogenin was isolated as a tumor angiogenic factor solely on the basis of its angiogenic activity. Its expression is essential for melanoma progression and metastasis. Many studies have mainly focused on how it induces angiogenesis, which allows further melanoma growth and metastasis. Here, we investigated the effects of angiogenin on melanoma cell growth and studied its influence on the expression and function of the basic fibroblast growth factor. We transfected the angiogenin gene in the sense and antisense orientation into A375 cells, and obtained stable angiogenin under-expressing and over-expressing transfectants. We found that in the angiogenin antisense transfectants, the cell proliferation was decreased and the basic fibroblast growth factor-induced cell proliferation was inhibited, but the expression of basic fibroblast growth factor was increased. In contrast, in the angiogenin sense transfectants, the cell proliferation was increased, and the basic fibroblast growth factor-induced cell proliferation was also increased. The expression of basic fibroblast growth factor, however, was decreased. In conclusion, we demonstrated that, besides its angiogenic activity, angiogenin also directly contributes to A375 cell proliferation and is required for the basic fibroblast growth factor to induce cell proliferation. We also demonstrated that the endogenous angiogenin expression levels affect the expression of basic fibroblast growth factor in A375 cells. By targeting angiogenin, therefore, one may find a potential therapeutic approach to human malignant melanoma.
血管生成素最初是仅基于其血管生成活性而作为肿瘤血管生成因子被分离出来的。其表达对于黑色素瘤的进展和转移至关重要。许多研究主要集中在它如何诱导血管生成，这使得黑色素瘤能够进一步生长和转移。在此，我们研究了血管生成素对黑色素瘤细胞生长的影响，并研究了其对碱性成纤维细胞生长因子表达和功能的影响。我们将有义及反义方向的血管生成素基因转染到A375细胞中，获得了血管生成素低表达和高表达的稳定转染子。我们发现，在血管生成素反义转染子中，细胞增殖减少，碱性成纤维细胞生长因子诱导的细胞增殖受到抑制，但碱性成纤维细胞生长因子的表达增加。相反，在血管生成素正义转染子中，细胞增殖增加，碱性成纤维细胞生长因子诱导的细胞增殖也增加。然而，碱性成纤维细胞生长因子的表达却减少了。总之，我们证明，除了其血管生成活性外，血管生成素还直接促进A375细胞增殖，并且是碱性成纤维细胞生长因子诱导细胞增殖所必需的。我们还证明，内源性血管生成素表达水平影响A375细胞中碱性成纤维细胞生长因子的表达。因此，通过靶向血管生成素，可能会找到一种治疗人类恶性黑色素瘤的潜在方法。
