NLRP3 inflammasomes in macrophages drive colorectal cancer metastasis to the liver

Qiaoting Deng; Yan Geng; Liying Zhao; Ru Li; Zhigao Zhang; Kun Li; Rongliang Liang; Xiangyang Shao; Maoliang Huang; Daming Zuo; Yingsong Wu; Qiang Ma

doi:10.1016/j.canlet.2018.10.030

NLRP3 inflammasomes in macrophages drive colorectal cancer metastasis to the liver

Cancer Lett. 2019 Feb 1:442:21-30. doi: 10.1016/j.canlet.2018.10.030. Epub 2018 Oct 28.

Authors

Qiaoting Deng¹, Yan Geng², Liying Zhao³, Ru Li⁴, Zhigao Zhang⁴, Kun Li⁴, Rongliang Liang⁵, Xiangyang Shao⁴, Maoliang Huang⁶, Daming Zuo⁷, Yingsong Wu⁸, Qiang Ma⁹

Affiliations

¹ Institute of Antibody Engineering, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou 510515, Guangdong, PR China; Clinical Core Laboratory, Center for Precision Medicine, Meizhou People's Hospital (Huangtang Hospital), Merzhou Hospital Affiliated to Sun Yat-sen University, Meizhou 514031, PR China.
² Department of Gastroenterology, 303 Hospital of People's Liberation Army, Nanning 530021, PR China.
³ Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, PR China.
⁴ Institute of Antibody Engineering, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou 510515, Guangdong, PR China.
⁵ Department of Laboratory Science, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong province, 510120, China.
⁶ Fuzhou Dingxiang Clinic, Fuzhou, Fujian 350028 China.
⁷ Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou 510515, Guangdong, PR China.
⁸ Institute of Antibody Engineering, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou 510515, Guangdong, PR China. Electronic address: [email protected].
⁹ Institute of Antibody Engineering, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou 510515, Guangdong, PR China. Electronic address: [email protected].

PMID: 30392787
DOI: 10.1016/j.canlet.2018.10.030

Abstract

Inflammation and immunity are important determinants of cancer initiation, promotion, and progression to cancer equilibrium or suppression. The NOD-like receptor family pyrin domain containing 3 (NLRP3) is an oligomeric intracellular immune receptor, and the main component of inflammasome. As a widely distributed effector of innate immunity, NLRP3 inflammasome affects development of many cancer types, but its exact role in colorectal cancer (CRC) is controversial. We found that cells with the macrophage (MΦ) marker CD68 and strong NLRP3 expression densely surrounded CRC tissue. The NLRP3 inflammasome was activated in MΦs by MΦ-CRC cell crosstalk; it resulted in faster migration of CRC cells, whereas blocking NLRP3 signaling suppressed CRC cell migration in vitro, and metastatic ability in vivo. NLRP3 signaling activation in MΦs can contribute to CRC cell migration and invasion.

Keywords: Colorectal cancer; Liver metastasis; Macrophage; NLRP3 inflammasome; Tumor microenvironment.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Movement*
Coculture Techniques
Colorectal Neoplasms / genetics
Colorectal Neoplasms / metabolism*
Colorectal Neoplasms / pathology
Culture Media, Conditioned / metabolism
Humans
Inflammasomes / metabolism*
Interleukin-1beta / metabolism
Liver Neoplasms / genetics
Liver Neoplasms / metabolism*
Liver Neoplasms / secondary
Macrophages / metabolism*
Macrophages / pathology
Male
Mice
Mice, 129 Strain
Mice, Inbred C57BL
Mice, Knockout
NLR Family, Pyrin Domain-Containing 3 Protein / deficiency
NLR Family, Pyrin Domain-Containing 3 Protein / genetics
NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
Neoplasm Invasiveness
Paracrine Communication*
Phenotype
Signal Transduction
THP-1 Cells

Substances

Culture Media, Conditioned
IL1B protein, human
IL1B protein, mouse
Inflammasomes
Interleukin-1beta
NLR Family, Pyrin Domain-Containing 3 Protein
NLRP3 protein, human
Nlrp3 protein, mouse