Novel strategies for cancer therapy targeting premetastatic niche

1. 结直肠癌肝转移的机制：我们使用微阵列技术比较了原发性结直肠癌和肝转移灶之间miRNA的表达差异。我们关注的是miR-122，与原发性肿瘤相比，miR-122在肝转移中上调最多，并且已被报道为肝脏特异性miRNA。免疫组化分析显示，miR-122靶基因阳离子氨基酸转运蛋白1（CAT1）在肝转移瘤中的表达水平明显低于原发肿瘤。此外，低CAT-1原发性结直肠癌患者的无转移生存期明显短于高CAT-1原发性结直肠癌患者。胃癌的脂质改变：我们使用成像质谱法比较了胃癌及其邻近非肿瘤性粘膜的脂质含量，发现钾内合磷脂酰胆碱（PC）（16:0 / 18:1）在癌灶中主要表达。已知溶血磷脂酰胆碱（LPC）在有酰基辅酶a存在的情况下通过LPCAT1在Lands循环中转化为PC。免疫组化分析显示，LPCAT1在肿瘤中高表达，主要在分化腺癌中。胃粘膜LPCAT1蛋白及其伴随的脂质改变似乎参与了胃癌的致癌或发展过程。

1. Mechanisms of colorectal liver metastasis : We compared difference in miRNA expression between primary colorectal cancers and their liver metastases using microarray. We focused on miR-122 which was the most up-regulated in liver metastases compared with primary tumors and has been reported as a liver-specific miRNA. Immunohistochemical analysis revealed that expression level of cationic amino acid transporter 1(CAT1), a target gene of miR-122, was significantly lower in liver metastases compared with primary tumors. Furthermore, patients with CAT-1 low primary colorectal cancer had significantly shorter liver metastasis-free survival than the patients with CAT-1 high tumors.2. Lipid alteration in gastric cancer : We compared the lipid content between gastric cancer and its adjacent non-neoplastic mucosa using imaging mass spectrometry and found that potassium-adducted phosphatidylcholine(PC)(16 : 0/18 : 1) was predominantly expressed in cancer lesions. Lysophosphatidylcholine(LPC) is known to be converted to PC in the presence of acyl-CoA by LPCAT1 in Lands' cycle. Immunohistochemical analysis revealed that LPCAT1 was highly expressed in cancer predominantly in differentiated adenocarcinoma. LPCAT1 protein and concomitant lipid alterations in gastric mucosa appear to be involved in the carcinogenic or developmental process of gastric cancer.