Oncotarget

Research Papers:

Antitumor effects of calgranulin B internalized in human colon cancer cells

Kun Kim, Kyung-Hee Kim, Kangsan Roh, Byong Chul Yoo _, Ja-Lok Ku, Young-Kyoung Shin, Jae Youl Cho, Minjae Kim, Myung-Hee Kwon, Sung Ho Goh, Hee Jin Chang and Jae Hwan Oh

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Oncotarget. 2016; 7:20368-20380. https://doi.org/10.18632/oncotarget.7783

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Abstract

Kun Kim1,2,*, Kyung-Hee Kim1,*, Kangsan Roh1,3,*, Byong Chul Yoo1, Ja-Lok Ku2,4, Young-Kyoung Shin2, Jae Youl Cho3, Minjae Kim5, Myung-Hee Kwon5, Sung Ho Goh6, Hee Jin Chang1,7, Jae Hwan Oh1,7

1Colorectal Cancer Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi, Republic of Korea

2Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea

3Department of Genetic Engineering, Sungkyunkwan University, Suwon, Republic of Korea

4Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea

5Department of Microbiology, Ajou University School of Medicine, Suwon, Republic of Korea

6Cancer Genomics Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi, Republic of Korea

7Center for Colorectal Cancer, National Cancer Center, Goyang, Gyeonggi, Republic of Korea

*These authors contributed equally to this work

Correspondence to:

Byong Chul Yoo, e-mail: [email protected]

Ja-Lok Ku, e-mail: [email protected]

Keywords: calgranulin B, colon cancer, protein internalization, inflammatory microenvironment, aurora A kinase

Received: October 08, 2015     Accepted: February 20, 2016     Published: February 27, 2016

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.


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