Genotechnologic Analysis of Control System of Proliferation and Metastasis by Gangliosides in Melanoma

我们利用从患者身上获得的细胞系和组织标本，研究了神经节苷类在黑色素瘤中的生物学功能。SK-MEL-28 （GD3和gm3阳性细胞系）的细胞增殖活性高于GD3缺陷突变克隆。具有新的神经节苷脂表达（GM3为主）的转移性黑色素瘤患者似乎比GM3和GD3水平均升高的患者生存时间更长。GD3被认为在肿瘤进展和预后中起关键作用。与亲本克隆（SK-MEL-28）相比，gd3缺陷细胞系α2β1和α3β1整合素受体的表达增加，对细胞外基质蛋白（包括I型和IV型胶原和层粘连蛋白）的粘附能力显著提高。SK-MEL-28中抗GDs单克隆抗体抑制了细胞对基质蛋白的附着。我们的研究结果表明神经节苷脂GM3（通过影响整合素受体水平）和GD3（通过直接与基质蛋白相互作用）可能在黑色素瘤的进展中发挥不同的生物学作用。

We investigated biological functions of gangliosides in melanoma using cell lines and tissue specimens obtained from the patients. SK-MEL-28 (GD3- and GM3-positive cell line) had higher activity of cell proliferation than its GD3-defecient mutant clone. Metastatic melanoma patients with the new ganglioside expression (GM3-predominant) seemed to survive longer than the ones with increased levels of both GM3 and GD3. GD3 was considered to have pivotal parts in concering tumor progression and prognosis. The GD3-deficient cell line, however, showed increased expression of α2β1 and α3β1 integrin receptors and significantly higher ability to adhere to extracellular matrix proteins including type I and IV collagens and laminin than the parent clone (SK-MEL-28). The treatment with monoclonal antibodies against GDs in SK-MEL-28 inhibited the cell attachment to the matrix proteins. Our findings suggest that gangliosides GM3 (by influencing integrin receptor levels) and GD3 (by interacting directly with matrix proteins) might play different biological roles in the progression of melanoma.