title: SPINK1 Status in Colorectal Cancer, Impact on Proliferation, and Role in Colitis-Associated Cancer.
abstract: 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.
  
  
  CONCLUSIONS
  Evidence suggests that SPINK1 is an important growth factor that connects chronic inflammation and cancer.
authors: Institute of Resource Development and Analysis, Kumamoto University, Kumamoto, Japan. Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors: Satoshi
authors: S
authors: Ida
authors: Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors: Nobuyuki
authors: N
authors: Ozaki
authors: Institute of Resource Development and Analysis, Kumamoto University, Kumamoto, Japan.
authors: Kimi
authors: K
authors: Araki
authors: Department of Digestive and General Surgery, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
authors: Kotaro
authors: K
authors: Hirashima
authors: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors: Yoko
authors: Y
authors: Zaitsu
authors: Institute of Resource Development and Analysis, Kumamoto University, Kumamoto, Japan. Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors: Katsunobu
authors: K
authors: Taki
authors: Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors: Yasuo
authors: Y
authors: Sakamoto
authors: Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors: Yuji
authors: Y
authors: Miyamoto
authors: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors: Eiji
authors: E
authors: Oki
authors: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors: Masaru
authors: M
authors: Morita
authors: Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
authors: Masayuki
authors: M
authors: Watanabe
authors: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors: Yoshihiko
authors: Y
authors: Maehara
authors: Institute of Resource Development and Analysis, Kumamoto University, Kumamoto, Japan.
authors: Ken-Ichi
authors: K
authors: Yamamura
authors: Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors: Hideo
authors: H
authors: Baba
authors: Institute of Resource Development and Analysis, Kumamoto University, Kumamoto, Japan. ohmuraya@kumamoto-u.ac.jp.
authors: Masaki
authors: M
authors: Ohmuraya
mesh_terms: D000368:Aged; D000818:Animals; D001397:Azoxymethane; D002352:Carrier Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D005260:Female; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007564:Japan; D008297:Male; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D029584:Prostatic Secretory Proteins / Q000378:metabolism; D014359:Trypsin Inhibitor, Kazal Pancreatic
chemical_list: D002352:Carrier Proteins; D006023:Glycoproteins; D029584:Prostatic Secretory Proteins; C486642:SPINK1 protein, human; C487134:Spink1 protein, mouse; D014359:Trypsin Inhibitor, Kazal Pancreatic; D016264:Dextran Sulfate; D001397:Azoxymethane