Molecular and clinical analysis for metastasis and invasion of cancers in small animals

小动物癌症转移和侵袭的分子和临床分析

• 批准号: 15208030
• 负责人: SASAKI Nobuo
• 金额: $ 33.53万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15208030/
• 关键词: canine mammary tumor cell line; feline mammary tumor cell line; canine mast cell tumor; adhesion molecule; retinoid; E-cadherin; microarray; metastasis; invasion; 犬乳癌細胞株; 猫乳癌細胞株; sLe(X); 細胞接着; E-Cadherin; sLe(x); E-cadherin; RARα; 乳癌細胞

In this study, we tried to analyze the mechanism of tumor metastasis and local invasion in small animals using 5 cell lines established in our laboratory.In canine mammary cancer, expression and function of E-cadherin and catenin were compared between 4 pairs of cell lines established from the primary or metastatic lesions of the same patients. As a result, there were no differences in their expression but their function was higher in cell lines established from the metastatic lesions than those from primary lesions. This may indicate that the cells in the metastasis with low E-cadherin function are easily released from the primary lesions. In addition, sLe(x), an adhesion molecule to the endothelial cells, was alos highly expressed in one of the cell lines established from the thoracic effusion due to metastasis. Our previous data showed sLe(x) was 60% positive in the mammary tumor tissues, but not in normal mammary gland. From these data, sLe(x) may play a role in the metastasis of c … More anine mammary tumors. Currently one of this mammary tumor cells was cloned and microarray analysis was conducted to clarify the genetic change in the cells from primary and metastatic lesions in nude mice model. The result may suggest some important molecules including NfκB and hipoxia related one, which will be analyzed in the future.In feline mammary tumors, we established 8 cell lines including 2 pairs from primary and metastatic lesions of the same patient. Using these cell lines, expression of a chemokine receptor CXCR4 and its ligand SDF-1 were compared between cell lines. Their expression was higher in those originated from metastasis than primary lesions, suggesting they may also play a role in tumor metastasis in feline mammary tumors. In addition, tumor-suppressing molecule, Braca2, was also analyzed in relation to the malignancy of this tumor.Retinoids, vitamin A derivatives, may control the growth of canine mast cell tumors. This tumor growth-inhibitory effect of retinoids against canine mast cell tumors was mediated by a receptor RAR alpha and via inducing apoptosis in both in vitro model and in vivo nude mice model, as in human acute promyelocytic leukemia. These results suggest the retinoids may be a potential chemotherapeutic agent for canine mast cell tumors. For canine osteosarcoma, gene therapy using wild type p53 transfection using adenovirus as a vector virus. This trial showed some efficacy in nude mice model and even in the canine patients with ostesarcoma. For canine melanoma, spindle check point function is currently investigated to analyze its relationship to chemotherapeutic response of the tumor. Less

本研究利用本实验室建立的5株乳腺癌细胞系，对犬乳腺癌原发灶和转移灶中E-cadherin和catenin的表达和功能进行了比较，并对E-cadherin和catenin在犬乳腺癌中的表达和功能进行了研究。结果，它们的表达没有差异，但它们的功能在从转移性病变建立的细胞系中高于从原发性病变建立的细胞系。这可能表明转移灶中E-cadherin功能低下的细胞容易从原发灶中释放出来。此外，内皮细胞粘附分子sLe（x）在由转移性胸腔积液建立的细胞系中也高度表达。我们以前的资料显示sLe（x）在乳腺癌组织中阳性率为60%，而在正常乳腺组织中不表达。从这些数据来看，sLe（x）可能在c ...更多信息 乳腺肿瘤。目前已克隆了其中一株乳腺癌细胞，并进行了基因芯片分析，以阐明裸鼠模型原发灶和转移灶细胞的遗传变化。本研究建立了8株猫乳腺肿瘤细胞系，其中2对来源于同一患者的原发灶和转移灶。使用这些细胞系，比较细胞系之间趋化因子受体CXCR 4及其配体SDF-1的表达。它们在转移灶中的表达高于原发灶，提示它们也可能在猫乳腺肿瘤的转移中起作用。此外，肿瘤抑制分子Braca 2也被分析与这种肿瘤的恶性程度有关。维甲酸，维生素A衍生物，可能控制犬肥大细胞瘤的生长。在体外模型和体内裸鼠模型中，类维生素A对犬肥大细胞肿瘤的这种肿瘤生长抑制作用是由受体RAR α介导的，并通过诱导细胞凋亡来实现，如在人急性早幼粒细胞白血病中一样。这些结果表明，类维生素A可能是一个潜在的治疗犬肥大细胞瘤的化疗药物。对于犬骨肉瘤，基因治疗采用野生型p53转染，以腺病毒为载体病毒。该试验在裸鼠模型中显示出一定的疗效，甚至在患有骨肉瘤的犬患者中也是如此。对于犬黑色素瘤，目前正在研究纺锤体检查点功能，以分析其与肿瘤化疗反应的关系。少

项目成果

Establishment of four pairs of canine mammary tumour cell lines derived from primary and metastatic origin and their E-cadherin expression

• DOI: 10.1111/j.1476-5810.2006.00098.x
• 发表时间: 2006-06-01
• 期刊: VETERINARY AND COMPARATIVE ONCOLOGY
• 影响因子: 2.1
• 作者: Uyama, R.;Nakagawa, T.;Sasaki, N.
• 通讯作者: Sasaki, N.

Oonuma T, Morimatsu M et al.: "Role of CXCR4 and SDF-1 in mammary tumor metastasis in the cat"J Vet Med Sci. 65. 1069-1073 (2003)

Oonuma T、Morimatsu M 等：“CXCR4 和 SDF-1 在猫乳腺肿瘤转移中的作用”J Vet Med Sci。

Identification and characterization of a canine highly similar to retinoic acid receptor alpha

与视黄酸受体α高度相似的犬科动物的鉴定和表征

• 发表时间: 2005
• 期刊: DNA Sequence 16
• 作者: Miyajima;N.;Watanabe;M.;Ohashi;E.;et al.
• 通讯作者: et al.

Analysis of genetic variations in the exon 27 region of the canine BRCA2 locus

• DOI: 10.1292/jvms.67.1013
• 发表时间: 2005-10-01
• 期刊: JOURNAL OF VETERINARY MEDICAL SCIENCE
• 影响因子: 1.2
• 作者: Yoshikawa, Y;Morimatsu, M;Hashizume, K
• 通讯作者: Hashizume, K

Retinoids induce growth inhibition and apoptosis in mast cell tumor cell lines

类维生素A诱导肥大细胞肿瘤细胞系的生长抑制和凋亡

• 发表时间: 2006
• 期刊: J. Vet. Med. Sci. 68
• 作者: Ohashi;E.;Miyajima;N.;Nakagawa;T.;et al.
• 通讯作者: et al.