Novel strategies for cancer therapy targeting premetastatic niche

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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.