Non-invasive in vivo analysis of early metastatic processes

早期转移过程的非侵入性体内分析

• 批准号: 09470506
• 负责人: OKU Naoto
• 金额: $ 7.62万
• 依托单位: University of Shizuoka
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470506/
• 关键词: metastasis; positron emission tomography (PET); cell trafficking; imaging; selectin; integrin; macrophage; metastasis suppresion; 転移標的組織; 免疫監視機構; ポジトロンCT (PET); シアリルルイスA; NR細胞; スルファチド; シアリルルイスX

For elucidating early phase of tumor metastasis, we developed non-invasive method to determine metastatic tumor cell trafficking by PET. We have already observed the correlation between metastatic potential and metastatic cell accumulation in a target tissues. In the present study, we firstly clarified the involvement of selectins in the early tumor cell trafficking. We also observed sulfatide, a ligand for selectins, suppressed tumor metastasis. Secondly, we investigated the role of integrins in tumor metastatic process by using integrin transfectants. CHO cells were transfected with a chain of integrins, I.e., α2, α3, α4, α6, α9 and av. PET analysis indicated that integrin αvβ1 and α4β1 enhanced tumor cell accumulation in a target tissue. Furthermore, useful evidences were obtained about involvement of integrin avb3 in liver metastasis. Thirdly, we investigated the role of immune surveillance on the suppression of tumor metastasis. If small number of tumor cells were injected in experimental metastatic model, metastasis was not observed due to removal of tumor cells from target by immune defense system. In fact, metastasis was observed in mice which were pretreated for the depletion of macrophages even when small number of tumor cells were injected. And, in this case, removal of tumor cells from target tissues was suppressed by the determination of PET. Therefore, we clearly demonstrated that macrophage play an important role for suppressing metastasis in the early stage of metastatic processes.

为了阐明肿瘤转移的早期阶段，我们开发了通过PET确定转移性肿瘤细胞运输的非侵入性方法。我们已经观察到转移潜能与靶组织中转移细胞积累之间的相关性。在本研究中，我们首先阐明了选择素在早期肿瘤细胞运输中的作用。我们还观察到硫苷脂，选择素的配体，抑制肿瘤转移。其次，我们利用整合素基因转染系统研究了整合素在肿瘤转移过程中的作用。CHO细胞用整联蛋白链转染，即，α2、α3、α4、α6、α9和av。PET分析表明，整合素αvβ1和α4β1增强肿瘤细胞在靶组织中的积聚。整合素avb3参与肝转移的研究也获得了有用的证据。第三，我们研究了免疫监视在抑制肿瘤转移中的作用。如果在实验转移模型中注射少量的肿瘤细胞，则由于免疫防御系统将肿瘤细胞从靶点移除而未观察到转移。事实上，即使在注射少量肿瘤细胞时，也在预处理以消耗巨噬细胞的小鼠中观察到转移。并且，在这种情况下，通过PET的测定抑制了肿瘤细胞从靶组织中的去除。因此，我们清楚地证明了巨噬细胞在转移过程的早期阶段对抑制转移起重要作用。

项目成果

Tomohiro Asai, et al.: "5'-O-dipalmitoylphosphatidyl 2'-C-Cyano-2'-deoxy-1-β-D-arabiono-pentofuranosyl-cytosine Is Enhanced by Long-circulating Liposomalization"Biol. Pharm. Bull.. 21. 766-771 (1998)

Tomohiro Asai 等人：“5-O-二棕榈酰磷脂酰 2-C-氰基-2-脱氧-1-β-D-阿拉伯-呋喃戊糖基-胞嘧啶通过长循环脂质体化得到增强”Biol Bull。 ..21.766-771 (1998)

Hironori Kikkawa, Daisei Miyamoto, Hidetoshi Imafuku, Chieko Koike, Yasuno Suzuki, Shoji Okada, Hideo Tsuka, Tatsuro Irimura and Naoto Oku: "Role of Sialylglycoconjugate(s) in the Initial Phase of Metastasis of Liver-metastatic RAW117 Lymphoma Cells."Jpn.

Hironori Kikkawa、Daisei Miyamoto、Hidetoshi Imafuku、Chieko Koike、Yasuno Suzuki、Shoji Okada、Hideo Tsuka、Tatsuro Irimura 和 Naoto Oku：“唾液酸糖复合物在肝转移性 RAW117 淋巴瘤细胞转移初始阶段的作用。”Jpn

Hironori Kikkawa,et al.: "Possible role immune surveillance at the initial phase of metastasis produced by B16BL6 melanoma cell"FEBS Lett.. 467. 211-216 (2000)

Hironori Kikkawa 等人：“免疫监视在 B16BL6 黑色素瘤细胞产生的转移初始阶段的可能作用”FEBS Lett.. 467. 211-216 (2000)

Dail Ishikawa, et al.: "GD1α-Replica peptides Functionally Mimic GD1 α, an Adhesion Molecule of Metastaric Tumor Cells, and Suppress the Tum or Metastasis"FEBS Lett.. 441. 20-24 (1998)

Dail Ishikawa 等人：“GD1α-复制肽功能性地模仿 GD1α（转移性肿瘤细胞的粘附分子）并抑制肿瘤或转移”FEBS Lett.. 441. 20-24 (1998)

Masako Takikawa, et al.: "Suppression of GD1 α ganglioside-mediated tum or metastasis by liposomalized WHW-peptide"FEBS Lett.. 466. 381-384 (2000)

Masako Takikawa 等：“通过脂质体化 WHW-肽抑制 GD1 α 神经节苷脂介导的肿瘤或转移”FEBS Lett.. 466. 381-384 (2000)