title: Antitumor effects of calgranulin B internalized in human colon cancer cells.
abstract: Calgranulin B is a small, calcium-binding protein expressed in neutrophils that is secreted into the tumor microenvironment in cancer cases. We previously showed that calgranulin B levels are increased in the stools of colorectal cancer patients. In patient tumor tissues, calgranulin B protein levels correlated with the presence of stromal inflammatory cells surrounding tumor cells, and calgranulin B promoter methylation was observed in both paired human tissues and colon cancer cell lines. Cell lines did not express calgranulin B, but in vitro studies showed that colon cancer cells internalized extracellular calgranulin B, while other types of cancer cells did not. Calgranulin B internalization led to reduced cell proliferation and increased apoptotic cell death. AKT and ERK signals were also increased after calgranulin B treatment, as were p53, β-catenin, E-cadherin and cleaved caspase-3 levels. Additionally, a human protein microarray identified aurora A kinase as a calgranulin B binding partner, and binding inhibited aurora A kinase activity in a dose-dependent manner. Our findings demonstrate the antitumor effects of calgranulin B in the inflammatory microenvironment and suggest that calgranulin B could be potentially efficacious in the treatment of colon cancer.
authors.affiliation: Colorectal Cancer Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi, Republic of Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Kun
authors.initials: K
authors.lastname: Kim
authors.affiliation: Colorectal Cancer Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi, Republic of Korea.
authors.forename: Kyung-Hee
authors.initials: KH
authors.lastname: Kim
authors.affiliation: Colorectal Cancer Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi, Republic of Korea.|Department of Genetic Engineering, Sungkyunkwan University, Suwon, Republic of Korea.
authors.forename: Kangsan
authors.initials: K
authors.lastname: Roh
authors.affiliation: Colorectal Cancer Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi, Republic of Korea.
authors.forename: Byong Chul
authors.initials: BC
authors.lastname: Yoo
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.|Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Ja-Lok
authors.initials: JL
authors.lastname: Ku
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Young-Kyoung
authors.initials: YK
authors.lastname: Shin
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon, Republic of Korea.
authors.forename: Jae Youl
authors.initials: JY
authors.lastname: Cho
authors.affiliation: Department of Microbiology, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Minjae
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Microbiology, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Myung-Hee
authors.initials: MH
authors.lastname: Kwon
authors.affiliation: Cancer Genomics Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi, Republic of Korea.
authors.forename: Sung Ho
authors.initials: SH
authors.lastname: Goh
authors.affiliation: Colorectal Cancer Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi, Republic of Korea.|Center for Colorectal Cancer, National Cancer Center, Goyang, Gyeonggi, Republic of Korea.
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Chang
authors.affiliation: Colorectal Cancer Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi, Republic of Korea.|Center for Colorectal Cancer, National Cancer Center, Goyang, Gyeonggi, Republic of Korea.
authors.forename: Jae Hwan
authors.initials: JH
authors.lastname: Oh
mesh_terms: D017209:Apoptosis; D064127:Aurora Kinases / Q000378:metabolism*; D040502:Calgranulin B / Q000378:metabolism*; D002453:Cell Cycle; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D059016:Tumor Microenvironment
chemical_list: D040502:Calgranulin B; D064127:Aurora Kinases
keywords: aurora A kinase; calgranulin B; colon cancer; inflammatory microenvironment; protein internalization