Role of Kallikrein 6 expression and secretion in colon cancer

描述（由申请人提供）：本提案将检验激肽释放酶6（KLK 6）蛋白在功能上参与结肠癌发生并可能是结肠癌发生的有用标志物的假设。我们已经证明：1）KLK 6蛋白可以在小鼠结肠和人结肠肿瘤中的腺瘤处检测到; 2）KLK 6功能阻断抗体减弱结肠癌细胞的侵袭;和3）KLK 6敲低的结肠癌细胞在SCID小鼠模型中不形成远处转移并增加动物存活率。为了验证这一假设，我们提出了以下具体目标：1）确定KLK 6在体内结肠癌进展中的作用; 2）确定KLK 6在结肠癌转移中的作用; 3）评估结肠中KLK 6蛋白表达和酶活性。该提案的主要目标是确定KLK 6在结肠肿瘤和转移形成中的作用，开发用于测量结肠中KLK 6酶活性的成像模式，并将其与疾病进展相关联。

DESCRIPTION (provided by applicant): This proposal will test the hypothesis that kallikrein 6 (KLK6) protein is functionally involved in, and may be a useful marker of, colon carcinogenesis. We have shown that: 1) KLK6 protein can be detected at the adenomas in the mouse colon, and in human colon tumors; 2) KLK6 function blocking antibody attenuates invasion of colon cancer cells; and 3) colon cancer cells with knockdown of KLK6 do not form distant metastases in SCID mouse model and increase animal survival rates. To test the overall hypothesis, we propose the following specific aims: 1) determine the role of KLK6 in the colon cancer progression in vivo; 2) determine the role of KLK6 in colon cancer metastasis; 3) evaluate KLK6 protein expression and enzymatic activity in the colon. The major objectives of this proposal are to determine the role of KLK6 in colon tumor and metastasis formation, develop an imaging modality for measuring of KLK6 enzymatic activity in the colon and correlate it with disease progression.