Review
Pharmacology & Pharmacy
Martine J. Smit, Geraldine Schlecht-Louf, Maria Neves, Jelle van den Bor, Petronila Penela, Marco Siderius, Francoise Bachelerie, Federico Mayor
Summary: The elevated expression of chemokine receptors CXCR4 and ACKR3 and their ligand CXCL12 in tumors and the tumor microenvironment has led to complex research on their contribution to cancer pathogenesis. Discussions include their impact on signaling networks, crosstalk with RTKs and other TME factors, as well as the infiltration of immune cells supporting tumor progression. Targeting the CXCL12/CXCR4/ACKR3 axis along with RTKs and immune cells modulation shows promising therapeutic potential in multitargeted cancer therapies.
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 61, 2021
(2021)
Review
Biochemistry & Molecular Biology
Mayara Bocchi, Nathalia de Sousa Pereira, Karen Brajao de Oliveira, Marla Karine Amarante
Summary: Migration of metastatic tumor cells is similar to the traffic of leukocytes and can be guided by chemokines and their receptors. The CXCL12/CXCR4 axis plays a crucial role in hematopoietic stem cell homing and supports malignant events. This axis serves as a communication bridge between tumor-stromal cells, creating a favorable microenvironment for tumor development, angiogenesis, and metastasis. This review explores the correlation between the CXCL12/CXCR4 axis and colorectal cancer, as well as potential therapeutic strategies.
MOLECULAR BIOLOGY REPORTS
(2023)
Review
Biochemistry & Molecular Biology
Yaru Yang, Jiayan Li, Wangrui Lei, Haiying Wang, Yunfeng Ni, Yanqing Liu, Huanle Yan, Yifan Tian, Zheng Wang, Zhi Yang, Shulin Yang, Yang Yang, Qiang Wang
Summary: Cancer is a complex disease caused by genetic mutations and/or epigenetic changes, and it poses the biggest challenge worldwide. Cytokines, particularly chemokines, play a significant role in various human cancers by affecting homeostasis, immune function, and facilitating cancer development stages such as invasion, metastasis, and angiogenesis. Specifically, chemokines such as CXCL12 and its receptors CXCR4 and CXCR7 exert extensive influence on tumor cell behavior, including proliferation, survival, angiogenesis, metastasis, and tumor microenvironment, making them crucial players in the initiation and progression of cancers such as leukemia, breast cancer, lung cancer, prostate cancer, and multiple myeloma. This review aims to summarize the recent research progress and future challenges related to the CXCL12-CXCR4/CXCR7 signaling axis in cancer, emphasizing the potential of utilizing CXCL12-CXCR4/CXCR7 as a biomarker or therapeutic target for cancer treatment and providing valuable insights for the development of targeted cancer therapies.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2023)
Article
Immunology
Paola Antonello, Diego U. Pizzagalli, Mathilde Foglierini, Serena Melgrati, Egle Radice, Sylvia Thelen, Marcus Thelen
Summary: Chemotaxis is an essential process in tumors metastasis, and in this study, ACKR3 was found to control the migration of lymphoma cells in response to CXCL12. The interaction between LTB4 and CXCL12 enhances the migration of lymphoma cells, providing a novel mechanism for cell-to-cell-induced migration.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Jan Philipp Schuette, Mailin-Christin Manke, Katherina Hemmen, Patrick Muenzer, Barbara F. Schoerg, Gustavo Campos Ramos, Michaela Pogoda, Valerie Dicenta, Sabrina H. L. Hoffmann, Juergen Pinnecker, Ferdinand Kollotzek, Monika Zdanyte, Karin A. L. Mueller, Yogesh Singh, Andreas F. Mack, Bernd Pichler, Florian Lang, Bernhard Nieswandt, Meinrad Gawaz, Katrin G. Heinze, Nicolas Casadei, Oliver Borst
Summary: Platelet-derived miRNAs play a critical role in myocardial inflammation and structural remodeling in response to myocardial ischemia/reperfusion (I/R). In a mouse model with a Dicer gene deletion, disrupted miRNA processing machinery in platelets led to increased myocardial inflammation, impaired angiogenesis, accelerated cardiac fibrosis, and larger infarct size. These findings highlight the importance of platelet-derived miRNA in regulating cellular processes following myocardial I/R.
CIRCULATION RESEARCH
(2023)
Article
Oncology
Christian Koch, Nina Charlotte Fischer, Malte Puchert, Juergen Engele
Summary: This study investigates the combined effects of CXCL12 and CXCL11 on specific tumor cells and reveals that their impact on cell migration, invasion, proliferation, and apoptosis depends on cell type and function. The findings suggest the potential limitations of targeting CXCR3, CXCR4, or CXCR7 selectively in cancer patients and highlight the importance of individualized targeting strategies.
Article
Pharmacology & Pharmacy
Mahdieh Mehrpouri
Summary: CXCL12/CXCR4 and CXCL12/CXCR7 axes play a key role in hematopoiesis and their aberrant expression may lead to the development of leukemia. Various therapeutic interventions have been developed to target these axes in leukemic cells, showing promising results in pre-clinical and clinical studies.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
David Schumacher, Elisa A. Liehn, Anjana Singh, Adelina Curaj, Erwin Wijnands, Sergio A. Lira, Frank Tacke, Joachim Jankowski, Erik A. L. Biessen, Emiel P. C. van der Vorst
Summary: The study found that CCR6 plays an important role in ischemia-reperfusion injury after acute myocardial infarction, exerting protective effects on the heart through bone marrow cells. Increasing CCR6-dependent immune mechanisms may represent an interesting therapeutic target for cardiac damage and inflammation.
Article
Immunology
Sofia R. Gardeta, Eva M. Garcia-Cuesta, Gianluca D'Agostino, Blanca Soler Palacios, Adriana Quijada-Freire, Pilar Lucas, Jorge Bernardino de la Serna, Carolina Gonzalez-Riano, Coral Barbas, Jose Miguel Rodriguez-Frade, Mario Mellado
Summary: The local lipid environment plays an important role in regulating CXCR4 organization and function, and modulating chemokine-triggered directed cell migration. Treatment of T cells with bacterial sphingomyelinase alters the lipid composition of the cell membrane, affecting membrane fluidity and CXCR4 nanoclustering and dynamics.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Eva M. Garcia-Cuesta, Jose Miguel Rodriguez-Frade, Sofia R. Gardeta, Gianluca D'Agostino, Pablo Martinez, Blanca Soler Palacios, Graciela Cascio, Tobias Wolf, Nicolas Mateos, Rosa Ayala-Bueno, Cesar A. Santiago, Pilar Lucas, Lucia Llorente, Luis M. Allende, Luis Ignacio Gonzalez-Granado, Noa Martin-Cofreces, Pedro Roda-Navarro, Federica Sallusto, Francisco Sanchez-Madrid, Maria F. Garcia-Parajo, Laura Martinez-Munoz, Mario Mellado
Summary: This study reveals that the truncated mutant chemokine receptor CXCR4(R334X) associated with WHIM syndrome fails to nanoclusterize after CXCL12 stimulation, affecting cell spatial organization and mobility, and causing multiple phalloidin-positive protrusions in cells. The inappropriate activation of beta-arrestin1 by CXCR4(R334X) leads to inadequate actin cytoskeleton remodeling, disrupting the balance between activated and deactivated cofilin.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell Biology
Peng Liu, Hongke Sun, Xin Zhou, Qiaozhu Wang, Feng Gao, Yuping Fu, Tong Li, Yixin Wang, Yingqi Li, Boyuan Fan, Xiaoli Li, Tiannan Jiang, Xinghua Qin, Qiangsun Zheng
Summary: This study identified three hub genes involved in atrial fibrillation (AF), with the CXCL12/CXCR4 axis standing out as a potent target for AF prevention. In vivo investigation showed that inhibiting CXCR4 reduced AF inducibility and duration by decreasing atrial inflammation and structural remodeling. Mechanistically, this effect was achieved by reducing immune cell recruitment and suppressing signaling pathways in the atria. These findings suggest that CXCL12/CXCR4 axis may be a potential therapeutic target for AF.
CELL DEATH & DISEASE
(2021)
Article
Oncology
Magali Merrien, Agata M. Wasik, Christopher M. Melen, Mohammad Hamdy Abdelrazak Morsy, Kristina Sonnevi, Henna-Riikka Junlen, Birger Christensson, Bjorn E. Wahlin, Birgitta Sander
Summary: Most lymphoma patients relapse after therapy due to hidden malignant cells in tissues protected by the microenvironment. The study focuses on the interaction between the biolipid 2-arachidonoylglycerol and the chemokine CXCL12 in lymphoma cell migration. The study demonstrates that 2-arachidonoylglycerol induces migration of B-lymphoma cells and affects the signaling pathways activated by CXCL12. The results suggest the previously unrecognized role of 2-arachidonoylglycerol in lymphoma cell mobilization.
Article
Biochemistry & Molecular Biology
Thaynan Lopes Goncalves, Luanna Prudencio de Araujo, Valeria Pereira Ferrer
Summary: The chemokine stromal cell-derived-factor 1 (SDF)-1/CXCL12 acts through its receptors CXCR4 and CXCR7, leading to cell survival, proliferation, and migration in breast cancer and glioblastoma. Tamoxifen (TMX), a selective estrogen receptor modulator, has shown potential antitumor activity against these tumors by inhibiting estrogen-regulated genes and targeting various proteins. This review discusses the role of the CXCL12-CXCR4-CXCR7 chemokine axis in tumor biology and suggests TMX as a potential modulator in breast cancer and a possible target in glioblastoma. Further studies on TMX's effect on the CXCL12-CXCR4-CXCR7 axis in glioblastoma could benefit patients, as this axis is associated with therapy resistance.
Article
Oncology
Crescenzo D'Alterio, Anna Spina, Laura Arenare, Paolo Chiodini, Maria Napolitano, Francesca Galdiero, Luigi Portella, Vittorio Simeon, Simona Signoriello, Francesco Raspagliesi, Domenica Lorusso, Carmela Pisano, Nicoletta Colombo, Gian Franco Zannoni, Nunzia Simona Losito, Rossella De Cecio, Giosue Scognamiglio, Daniela Califano, Daniela Russo, Valentina Tuninetti, Maria Carmela Piccirillo, Piera Gargiulo, Francesco Perrone, Sandro Pignata, Stefania Scala
Summary: Despite advances in research on epithelial ovarian cancer, this study systematically evaluated the CXCR4-CXCL12-CXCR7 axis in tumor and stromal cells, identifying a potential prognostic and therapeutic target in high CXCL12 expression in cancer cells. The study highlights the importance of further investigating the CXCL12 axis to improve treatment efficacy in EOC patients.
Article
Cell Biology
Liam A. Ridge, Dania Kewbank, Dagmar Schuetz, Ralf Stumm, Peter J. Scambler, Sarah Ivins
Summary: The study shows that CXCL12 signaling through its receptor CXCR4 plays distinct roles in different stages of SLV development, guiding cellular distribution and regulating cell proliferation. The atypical chemokine receptor CXCR7 may have a role in regulating ligand bioavailability during SLV morphogenesis.
