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: 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, Jae Hwan Oh
• Journal: Oncotarget (Oncotarget) Vol. 7 Issue 15 Pg. 20368-80 (Apr 12 2016) ISSN: 1949-2553 [Electronic] United States
• PMID: 26933915 (Publication Type: Journal Article)

Chemical References

• Calgranulin B
• Aurora Kinases

Topics

• Apoptosis
• Aurora Kinases (metabolism)
• Calgranulin B (metabolism)
• Cell Cycle
• Cell Proliferation
• Colonic Neoplasms (metabolism, pathology)
• Humans
• Signal Transduction
• Tumor Cells, Cultured
• Tumor Microenvironment