Chemoattractant GPCR Assays
Background of Chemotactic Receptors
Chemotactic receptors are a family of seven transmembrane G protein-coupled receptors (GPCRs) that were originally found primarily on leukocytes. According to their ligand sources and expression patterns, members of this family are divided into canonical GPCRs and chemokine GPCRs. The former includes platelet-activating factor receptor (PAFR), formyl peptide receptors and their variants (FPR1, FPR2, and FPR3), leukotriene B4 receptors and their variants (BLT1 and BLT2), and activating complement component 5a receptors (C5aR). Chemokine GPCRs consist of four subfamilies and are therefore referred to as CCR, CXCR, CX3CR, and XCR.
Fig.1. The multiple roles of chemoattractant GPCRs in tumor. (Huang, 2008)
Function of Chemotactic Receptors
The expression levels of chemotactic receptors depend on the level of neutrophil maturation and activation state. Accumulating evidence further suggests that chemotactic GPCRs contribute to development, invasion, homeostasis, angiogenesis/vascular inhibition, and metastasis. In addition, the multiple properties of GPCRs in the progression of malignant tumors make them targets for the development of novel antitumor therapeutics.
Mechanisms of Chemotactic Receptors
Activated chemotactic GPCRs initiate a series of signaling pathways, such as phospholipase C (PLC), protein kinase C (PKC), Ca2+, and MAPK, to regulate leukocyte activation and migration.
| Receptor | Gene | Mechanism | Agonists | Antagonists |
| Chemerin receptor 1 | CMKLR1 |
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| Chemerin receptor 2 | CMKLR2 |
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| Assay No. | Assay Name | Host Cell | Assay Type | Datasheet |
|---|---|---|---|---|
| Radioligand Binding Assay | ||||
| S01YF-1122-KX280 | Magic™ Human CMKLR2 In Vitro Radioligand Binding Assay | CHO-K1 | Radioligand Binding Assay | |
Published Data
| Paper Title | Chemokine/GPCR Signaling-Mediated EMT in Cancer Metastasis |
| Journal | Journal of Oncology |
| Published | 2022 |
| Abstract | Metastasis is considered a key factor leading to cancer-related death and is associated with epithelial-mesenchymal transition (EMT). In tumors, chemokine/GPCR signaling can trigger EMT, but the relationship between chemokine/GPCR signaling-mediated EMT and metastasis remains unclear. Based on studies of GPCR signaling, several potential pathways that might contribute to EMT have been proposed, including signaling mediated by β-arrestin, dimerization activation, G protein, and transactivation. However, the evidence supporting the contribution of EMT to metastasis remains limited. The answer to this question provides a new direction for fighting cancer metastasis. |
| Result |
Based on the premise of calcium-mediated p-EMT, the researchers proposed that different signals induced by chemokine receptors may be involved in different EMT programs. Researchers have advanced in understanding of chemokine-triggered signaling and the EMT program, but further exploration is needed on how different chemokines and signaling pathways work together to drive EMT in different tumors. Chemokines play a key role in metastatic dissemination by being intimately involved in cell migration, mediating cell adhesion, and recruiting immune cells. Uncovering how cancer cells control chemokine receptors to mediate cell migration is a promising strategy for cancer therapy.
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Fig.2. Interaction between cancer cells and non-cancer cells via chemokine. (Tian, 2022)
References
- Huang, J.; et al. G-protein coupled chemoattractant receptors and cancer. Frontiers in bioscience: a journal and virtual library. 2008; 13: 3352.
- Tian, X.; et al. Chemokine/GPCR Signaling-Mediated EMT in Cancer Metastasis. Journal of Oncology. 2022.
