RRC ID 67427
Author Ida S, Ozaki N, Araki K, Hirashima K, Zaitsu Y, Taki K, Sakamoto Y, Miyamoto Y, Oki E, Morita M, Watanabe M, Maehara Y, Yamamura K, Baba H, Ohmuraya M.
Title SPINK1 Status in Colorectal Cancer, Impact on Proliferation, and Role in Colitis-Associated Cancer.
Journal Mol Cancer Res
Abstract UNLABELLED:Colorectal cancer 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 colorectal cancer, the details remain 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 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.
IMPLICATIONS:Evidence suggests that SPINK1 is an important growth factor that connects chronic inflammation and cancer.
Volume 13(7)
Pages 1130-8
Published 2015-7-1
DOI 10.1158/1541-7786.MCR-14-0581
PII 1541-7786.MCR-14-0581
PMID 25804623
MeSH Aged Animals Azoxymethane Carrier Proteins / metabolism* Cell Line, Tumor Cell Proliferation* Colitis / chemically induced Colitis / metabolism* Colonic Neoplasms / etiology Colonic Neoplasms / metabolism Colonic Neoplasms / pathology Colorectal Neoplasms / chemically induced Colorectal Neoplasms / metabolism* Colorectal Neoplasms / pathology Dextran Sulfate Disease Models, Animal Female Glycoproteins / metabolism Humans Inflammation / metabolism Japan Male Mice, Inbred C57BL Middle Aged Prostatic Secretory Proteins / metabolism Trypsin Inhibitor, Kazal Pancreatic
IF 4.63
Human and Animal Cells COLO205(RCB2127) HCT116(RCB2979)