SPINK1 Status in Colorectal Cancer, Impact on Proliferation, and Role in Colitis-associated Cancer
Menée in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels une surexpression de la protéine SPINK1 favorise la prolifération des cellules cancéreuses dans le côlon
Colorectal cancer (CRC) is a major cause of deaths due to cancer; therefore, research into its etiology is urgently needed. Although it is clear that chronic inflammation is a risk factor for CRC, the details remains uncertain. Serine protease inhibitor Kazal type 1 (SPINK1) is mainly produced in pancreatic acinar cells. However, SPINK1 is expressed in various cancers and in inflammatory states such as colon cancer and inflammatory bowel disease. There are structural similarities between SPINK1 and epidermal growth factor (EGF). Hence, it was hypothesized that SPINK1 functions as a growth factor for tissue repair in inflammatory states, and if prolonged, acts as a promoter for cell proliferation in cancerous tissues. Here, immunohistochemical (IHC) staining for SPINK1 was observed in a high percentage of CRC 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 (AOM) and nongenotoxic carcinogen dextran sodium sulfate (DSS) 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 CRC progression. Implications: Evidence suggests that SPINK1 is an important growth factor that connects chronic inflammation and cancer.