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

本研究利用本实验室建立的5个细胞系，对小动物肿瘤转移和局部侵袭的机制进行了研究，并对同一患者原发灶和转移灶建立的4对细胞系中E-钙粘附素和连环蛋白的表达和功能进行了比较。因此，在转移灶建立的细胞系中，它们的表达没有差异，但其功能高于原发灶建立的细胞系。这可能表明E-钙粘附素功能低下的转移灶中的细胞容易从原发灶中释放出来。此外，在胸腔积液转移所建立的一种细胞系中，内皮细胞的黏附分子SLE(X)也高表达。我们以前的数据显示，SLE(X)在乳腺肿瘤组织中阳性率为60%，而在正常乳腺组织中不阳性。从这些数据来看，sle(X)可能在c-…的转移中起作用。更多的阿宁乳房肿瘤。目前已克隆了其中一种乳腺肿瘤细胞，并通过基因芯片分析，阐明了裸鼠模型原发和转移瘤细胞的遗传变化。这一结果可能提示了一些重要的分子，包括核因子κB和缺氧相关分子，将在未来进行分析。在猫乳腺肿瘤中，我们建立了8个细胞系，其中2对来自同一患者的原发灶和转移灶。利用这些细胞系，比较了趋化因子受体CXCR4及其配体SDF-1在不同细胞系中的表达。它们在转移性病变中的表达高于原发灶，提示它们在猫乳腺肿瘤的肿瘤转移中也可能起作用。此外，还分析了肿瘤抑制分子BRACA2与该肿瘤的恶性程度的关系。维甲酸，维生素A的衍生物，可能控制犬肥大细胞肿瘤的生长。与人急性早幼粒细胞白血病一样，维甲酸对犬肥大细胞肿瘤的这种生长抑制作用是通过RARα受体介导的，并通过在体外模型和体内裸鼠模型中诱导细胞凋亡来实现的。这些结果表明，维甲酸可能是治疗犬肥大细胞瘤的潜在化疗药物。对于犬骨肉瘤，以腺病毒为载体病毒，采用野生型p53基因治疗。本实验在裸鼠模型上，甚至在犬骨肉瘤患者身上都显示出了一定的疗效。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。较少

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