Investigation of molecular pathway of SPINK1 in colorectal cancer and its application to new molecular target therapy

2015 Fiscal Year Final Research Report

• Project/Area Number: 25861196
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Japanese Foundation for Cancer Research (2014-2015); Kumamoto University (2013)
• Principal Investigator: Ida Satoshi 公益財団法人がん研究会, その他部局等, その他 (80583038)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: SPINK1 / 大腸癌 / EGFR

Outline of Final Research Achievements

Serine protease inhibitor, Kazal type 1 (SPINK1) is mainly produced in pancreatic acinar cells. However, SPINK1 is expressed in various cancers and inflammatory states, such as colon cancer and inflammatory bowel disease. There are structural similarities between SPINK1 and epidermal growth factor (EGF).
Here, immunohistochemical staining for SPINK1 was observed in a high percentage of colorectal cancer patient specimens and SPINK1 induced proliferation of human colon cancer cell lines. To clarify its role in colon cancer in vivo, a mouse model exposed to the colon carcinogen azoxymethane and nongenotoxic carcinogen dextran sodium sulfate revealed that Spink3 (mouse homolog of SPINK1) is overexpressed in cancerous tissues. In Spink3 heterozygous mice, tumor multiplicity and tumor volume were significantly decreased compared with wild-type mice. These results suggest that SPINK1/Spink3 stimulates the proliferation of colon cancer cells and is involved in colorectal cancer progression.

Free Research Field

消化器外科