The molecular structure and role of LECT2 or CHM‐II in arthritis, cancer, and other diseases

Abstract

Leukocyte cell-derived chemotaxin-2 (LECT2 or LECT-2), also called chondromodulin II (ChM-II or CHM2) plays a versatile role in various tissues. It was first identified as a chemotactic factor to promote the migration of neutrophils. It was also reported as a hepatokine to regulate glucose metabolism, obesity, and nonalcoholic fatty liver disease. As a secreted factor, LECT2 binds to several cell surface receptors CD209a, Tie1, and Met to regulate inflammatory reaction, fibrogenesis, vascular invasion, and tumor metastasis in various cell types. As an intracellular molecule, it is associated with LECT2-mediated amyloidosis, in which LECT2 misfolding results in insoluble fibrils in multiple tissues such as the kidney, liver, and lung. Recently, LECT2 was found to be associated with the development of rheumatoid arthritis and osteoarthritis, involving the dysregulation of osteoclasts, mesenchymal stem cells, osteoblasts, chondrocytes, and endothelial cells in the bone microenvironment. LECT2 is implicated in the development of cancers, such as hepatocellular carcinoma via MET-mediated PTP1B/Raf1/ERK signaling pathways and is proposed as a biomarker. The mechanisms by which LECT2 regulates diverse pathogenic conditions in various tissues remain to be fully elucidated. Further research to understand the role of LECT2 in a tissue tropism-dependent manner would facilitate the development of LECT2 as a biomarker for diagnosis and therapeutic target.

Comprehensive analysis of SLC43A2 on the tumor immune microenvironment and prognosis of liver hepatocellular carcinoma

“…PGLYRP4 plays a role in inflammation and immune cell recruitment (Dabrowski et al, 2019;Karami et al, 2021). LECT2 inhibits the tumorigenicity of the LIHC cells in vivo (Zhu et al, 2022;Ong et al, 2011). This risk score model was developed using the TCGA-LIHC cohort and validated using the ICGC-LIRI-JP cohort.…”

Identification of lncRNAs and immune-related prognostic genes as thyroid cancer microenvironment biomarkers

“…LECT2 plays important role in a wide variety of various organizations. LECT2 is involved in the development of cancers such as liver cancer through the Met-mediated PTP1B/Raf1/ERK signaling pathway and is considered to be a biomarker [17]. CSF3 is a cytokine present in and outside cells involved in immune-related responses.…”

Organokines in Rheumatoid Arthritis: A Critical Review

“…More recently, this hepatokine was correlated with regulatory actions on glucose metabolism, obesity, and the development of non-alcoholic fatty liver diseases. It also promotes fibrogenesis, vascular invasion, and tumor metastasis in cancer of various cell types [ 129 , 130 , 131 ].…”

“…Other polymorphisms are responsible for the dysregulation of osteoclasts, osteoblasts, chondrocytes, endothelial cells, and mesenchymal stem cells in RA pathophysiology although these polymorphisms are still not known. The dysregulation of these cell joints is derived from the influx of pro-inflammatory immune cells to the articular spaces, increasing pro-inflammatory cytokines, such as IL-1β and IL-6, which are associated with bad joint prognostics in RA [ 104 , 105 , 130 , 131 , 132 ].…”