title: Tissue inhibitor of metalloproteinases-3 transfer suppresses malignant behaviors of colorectal cancer cells.
abstract: Colorectal carcinoma is one of the most frequent cancer diseases. For patients with this type of cancer, liver metastases are the main cause of death. Therefore, new therapeutic approaches are urgently needed to improve the outcomes. We found that both mRNA and protein levels of tissue inhibitor of metalloproteinase-3 (TIMP3) were decreased significantly in colorectal cancer tissue when compared with normal mucosa, suggesting that decrease of TIMP3 expression was correlated with malignant behavior of colorectal cancer. We evaluated the power of TIMP3, a new potent multiple functional molecule, as a biotheropeutic tool to treat cancer. Adenovirus-mediated TIMP3 transduction in CT26 colon cancer model demonstrated multiple effects to arrest cancer cell growth and induced massive apoptosis. Also, adenovirally transferred TIMP3 reduced adhesion, migration and invasion behaviors of CT26 cells in vitro. In vivo data showed that TIMP3 suppressed in vivo tumor growth and that liver metastasis was significantly reduced by TIMP3 transduction. This is the first systematic preclinical study to show that TIMP3 may be a potential molecular tool for colon cancer biological therapy.
authors.affiliation: Department of Gastroenterology Surgery, Peking University People's Hospital, Beijing, China.
authors.forename: H
authors.initials: H
authors.lastname: Lin
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.forename: D
authors.initials: D
authors.lastname: Xu
authors.forename: X
authors.initials: X
authors.lastname: Meng
authors.forename: Y
authors.initials: Y
authors.lastname: Shao
authors.forename: C
authors.initials: C
authors.lastname: Lin
authors.forename: Y
authors.initials: Y
authors.lastname: Ye
authors.forename: H
authors.initials: H
authors.lastname: Qian
authors.forename: S
authors.initials: S
authors.lastname: Wang
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D007120:Immunochemistry; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D046888:Tissue Array Analysis; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D012333:RNA, Messenger; C088390:TIMP3 protein, human; D019717:Tissue Inhibitor of Metalloproteinase-3; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9