Increased expression of the chemokine CCL2 in tumor cells correlates with enhanced metastasis, poor prognosis, and recruitment of CCR2(+)Ly6C(hi) monocytes. However, the mechanisms driving tumor cell extravasation through the endothelium remain elusive. Here, we describe CCL2 upregulation in metastatic UICC stage IV colon carcinomas and demonstrate that tumor cell-derived CCL2 activates the CCR2(+) endothelium to increase vascular permeability in vivo. CCR2 deficiency prevents colon carcinoma extravasation and metastasis. Of note, CCR2 expression on radio-resistant cells or endothelial CCR2 expression restores extravasation and metastasis in Ccr2(-/-) mice. Reduction of CCR2 expression on myeloid cells decreases but does not prevent metastasis. CCL2-induced vascular permeability and metastasis is dependent on JAK2-Stat5 and p38MAPK signaling. Our study identifies potential targets for treating CCL2-dependent metastasis.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ccr.2012.05.023 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Single-cell transcriptomics identifies the common perturbations of monocyte/macrophage lineage cells in inflammaging of bone marrow.
J Orthop Translat
January 2025
Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China.
Background: Bone marrow inflammaging is a low-grade chronic inflammation that induces bone marrow aging. Multiple age-related and inflammatory diseases involve bone marrow inflammaging. Whether common pathological pathways exist in bone marrow inflammaging remains unclear.
View Article and Find Full Text PDFComplement C3 of tumor-derived extracellular vesicles promotes metastasis of RCC via recruitment of immunosuppressive myeloid cells.
Proc Natl Acad Sci U S A
January 2025
Zhongda Hospital, School of Life Sciences and Technology, Advanced Institute for Life and Health, Southeast University, Nanjing 210096, China.
Heterogeneous roles of complement C3 have been implicated in tumor metastasis and are highly context dependent. However, the underlying mechanisms linking C3 to tumor metastasis remain elusive in renal cell carcinoma (RCC). Here, we demonstrate that C3 of RCC cell-derived extracellular vesicles (EVs) contributes to metastasis via polarizing tumor-associated macrophages (TAMs) into the immunosuppressive phenotype and recruiting polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs).
View Article and Find Full Text PDFBlood immunophenotyping of multiple sclerosis patients at diagnosis identifies a classical monocyte subset associated to disease evolution.
Front Immunol
January 2025
Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Recherche U1236, Université Rennes, Etablissement Français du Sang Bretagne, LabEx IGO, Rennes, France.
Introduction: Myeloid cells trafficking from the periphery to the central nervous system are key players in multiple sclerosis (MS) through antigen presentation, cytokine secretion and repair processes.
Methods: Combination of mass cytometry on blood cells from 60 MS patients at diagnosis and 29 healthy controls, along with single cell RNA sequencing on paired blood and cerebrospinal fluid (CSF) samples from 5 MS patients were used for myeloid cells detailing.
Results: Myeloid compartment study demonstrated an enrichment of a peculiar classical monocyte population in 22% of MS patients at the time of diagnosis.
Slamming hepatocellular carcinoma: targeting immunosuppressive macrophages via SLAMF7 reprograms the tumor microenvironment.
Transl Cancer Res
December 2024
Department of Hepatology and Gastroenterology, Campus Charité Mitte and Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer and one of the leading causes of cancer-related deaths worldwide due to limited treatment options. The tumor microenvironment (TME), which is usually immunosuppressive in HCC, appears to be a decisive factor for response to immunotherapy and strategies aimed at inducing a more inflamed TME hold promise to overcome resistance to immunotherapy. Within the TME, the interplay of various cell types determines whether immunotherapy is successful.
View Article and Find Full Text PDFSMR-guided molecular subtyping and machine learning model reveals novel prognostic biomarkers and therapeutic targets in non-small cell lung adenocarcinoma.
Sci Rep
January 2025
Department of Surgical Oncology II, The General Hospital of Ningxia Medical University, 804 Shengli Street, Yinchuan, Ningxia, 750004, China.
Non-small cell lung adenocarcinoma (LUAD) is a markedly heterogeneous disease, with its underlying molecular mechanisms and prognosis prediction presenting ongoing challenges. In this study, we integrated data from multiple public datasets, including TCGA, GSE31210, and GSE13213, encompassing a total of 867 tumor samples. By employing Mendelian randomization (MR) analysis, machine learning techniques, and comprehensive bioinformatics approaches, we conducted an in-depth investigation into the molecular characteristics, prognostic markers, and potential therapeutic targets of LUAD.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!