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

神经节苷脂对黑色素瘤增殖和转移控制系统的基因技术分析

• 批准号: 10670793
• 负责人: SHIMIZU Takahiro
• 金额: $ 0.45万
• 依托单位: Yamaguchi University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670793/
• 关键词: Malignant melanoma; Ganglioside; SK-MEL-28; GD3-positive cell; GD3-deficient melanomma cell line; Cell proliferation; Extracellular matrix protein; Cell attachment; GD3欠損ヒト黒色腫変異細胞株N2; GD3合成酵素cDNA; トランスフェクト

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.

我们使用从患者获得的细胞系和组织标本研究了神经毒剂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其GD3不熟悉的突变体克隆。新的神经节苷脂表达（GM3-促销）的转移性黑色素瘤患者似乎比GM3和GD3水平升高的转移性黑色素瘤的生存时间更长。 GD3被认为具有有关肿瘤进展和进展的关键部分。然而，GD3缺乏细胞系显示了α2β1和α3β1整合素受体的表达增加，并且比亲本克隆（SK-MEL-28）粘附在包括I型和IV胶原和层粘连蛋白（IV型胶原蛋白和层粘连蛋白）的能力上明显更高。在SK-MEL-28中对GDS的单克隆抗体进行治疗抑制了细胞附着基质蛋白。我们的发现表明，神经节的GM3（通过影响者整联蛋白受体水平）和GD3（通过与基质蛋白直接相互作用）可能在黑色素瘤进展中起不同的生物学作用。

项目成果

Nakano J: "Lack of Induction of Anti-Gangrioside GM_3 antibody in the Patients with Maignant Melanoma in Japanese"Pigment Cell Research. 11. 213-215 (1998)

Nakano J：“日本恶性黑色素瘤患者缺乏抗神经节苷脂 GM_3 抗体的诱导”色素细胞研究。

Nakano J: "Lack of Induction of Anti-Gangrioside GM_3 antibody in the Patients with Malignant Melanoma in Japanese"Pigment Cell Research. 11. 213-215 (1998)

Nakano J：“日本恶性黑色素瘤患者缺乏抗神经节苷脂 GM_3 抗体的诱导”色素细胞研究。

Nakano, J., et al: "Lack of Induction of Anti-Gangrioside GMィイD23ィエD2 antibody in the Patients with Malignant Melanoma in Japanese"Pigment Cell Research. 11. 213-215 (1998)

Nakano, J., et al:“日本恶性黑色素瘤患者缺乏抗神经节苷脂 GM-D23-D2 抗体的诱导”Pigment Cell Research 11. 213-215 (1998)。

武藤正彦: "ヒトメラノーマの分子疫学"腫瘍マーカー研究会誌(電子ジャーナル). (掲載予定). (2000)

Masahiko Muto：“人类黑色素瘤的分子流行病学”肿瘤标志物研究学会杂志（电子期刊）（2000 年）。

Nakano, J., et al: "Biologic Roles of Gangrioside GMィイD23ィエD2 and GDィイD23ィエD2 in the Attachment of Human Melanoma Cells to Extramatrix Proteins"Journal of Investigative Dermatology Symposium Proceedings. 4. 173-176 (1999)

Nakano, J. 等人：“神经节苷脂 GM 和 GD 在人类黑色素瘤细胞与基质外蛋白附着中的生物学作用”《皮肤病学研究杂志》研讨会论文集 4. 173-176 (1999)。