PMCID string | Title string | Sentences string |
|---|---|---|
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | In neoplasms, the chemokine system plays a promiscuous role depending on the type of cancer, the cellular and environmental context, and the involved chemokine axis. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | The chemokine system can influence disease progression in a beneficial or detrimental way (14–21). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | In many solid cancers altered expression levels of ACKR3 correlate with poor prognosis and tumor metastasis (22–29). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | In addition, the CXCL12/ACKR3/CXCR4 axis was proposed to be involved in lymphoma (30–32). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Diffuse large B cell lymphoma (DLBCL) arise in the germinal center when B cells undergo somatic hypermutation and class-switch recombination. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | During these events, genetic alterations can cause malignant tumor transformation leading to GC-derived B cell lymphoma (33). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | We have previously shown that GC derived DLBCL VAL cells, require the functional expression of ACKR3 to disseminate into distant organs in NOD/SCID mice (32). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Tumor spreading is a multistage process where cancer cells undergo transformation, leave the primary tumor and migrate into adjacent and distant tissues, where they proliferate (34–38). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | It was previously assumed that cancers metastasize through single tumor cells escaping from the primary site arriving at distant tissues and propagating there. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | However, in the last decade, emerging evidence suggests that metastases can disseminate with a more complex mechanism called collective cell migration (39). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | This process describes the presence of leading cells that trace the way into adjacent tissues for the migration of follower cells (40) or induce the movement of cohesive clusters (39). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Collective migration has been extensively studied to describe the metastasis of solid tumors but is seldom used to describe the movement of hematological cancers in a contact independent manner. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Through chemokine sequestration expression of scavenger receptors can contribute to the formation of self-generated gradients (40, 41). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | The mechanisms by which ACKR3, CXCR4 and CXCL12 induce the dissemination of VAL cells in a synergetic manner have not been addressed. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Here, we demonstrate that in the presence of CXCL12 wild type VAL cells (VAL-wt), which can express ACKR3 on the cell surface, create cues that in vitro can be sensed by CXCR4 follower VAL-wt. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Moreover, VAL-wt support in vitro chemotaxis of VAL cells in which ACKR3 was genetically deleted (VAL-ko). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | The latter by themselves are not able to migrate in response to CXCL12. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | In vivo VAL-wt can induce the migration of CXCR4 VAL-ko, contributing to the infiltration of draining lymph nodes. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Using a novel computational analysis of 3D migration, we show that in the presence of CXCL12 VAL-wt stimulate cell-to-cell-induced migration presumably through the release of leukotriene B4 (LTB4). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Moreover, the release of LTB4 from VAL cells induces cell polarization and chemotaxis in an autocrine and paracrine fashion. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | We propose a novel mechanism by which ACKR3 sustains the movement of otherwise migration incompetent cells and partially reveal the molecular components of this pathway. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | The atypical chemokine receptor ACKR3 is known to be upregulated on both solid cancers and blood neoplasms (22, 24, 30, 31). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Here we investigated its expression and functionality on two DLBCL lines, VAL and DOHH2. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Flow cytometry was performed on wild type DLBCL cells and VAL cells in which ACKR3 was genetically ablated (VAL-ko). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | In the cells with deleted ACKR3 cyan fluorescent protein (CFP) was introduced under constitutively active spleen focus-forming virus (SFFV) promoter, which allows to easily identify cells in tissues and mixed cultures (32). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | We measured surface expression on these cells of ACKR3, CXCR4 and CCR7. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | All cells expressed similar levels of CXCR4 on the plasma membrane ( Figure 1A ). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Conversely, ACKR3 was expressed only on a fraction of VAL-wt (10-18%), despite their clonal nature and continuous mRNA levels of the receptor (32). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | When cells were sorted for ACKR3 surface expression and cultured, the mixed phenotype reestablished rapidly within 2-3 weeks. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | However, cells negative for ACKR3 at sorting were more refractory for acquiring ACKR3 surface expression during this time ( Figure S1A ). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | However, during prolonged culture (6 weeks) the cell established the initial phenotype. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Similarly, only a small fraction of DOHH2 expressed ACKR3 on the plasma membrane ( Figure 1A ). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Interestingly, CCR7 was predominantly expressed on the surface of wild type DLBCL (VAL-wt and DOHH2), which were negative for ACKR3 plasma membrane expression. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Genetic deletion of ACKR3 on VAL cells had no effect on CXCR4 expression. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Surprisingly, CCR7 transcripts were less frequent in VAL-ko (117 ± 23 vs. 898 ± 32, (n=5)) and surface expression was markedly reduced on VAL-ko ( Figure 1A ). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Chemokine receptor expression and function on DLBCL cells. ( |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | ACKR3 (mAb 11G8), CXCR4 (mAb 12G5) and CCR7 (mAb G043H7) surface expression on VAL-wt, DOHH2, and VAL-ko was measured by flow cytometry. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Representative plots of three independent experiments. ( |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Uptake of the chimeric chemokine CXCL11_12 AF647 by DLBCL. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Mean fluorescence intensity (MFI) of DLBCL incubated with 50 nM of CXCL11_12 for 45 min at 37°C. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | MFI (by flow cytometry) reports the mean ± SD (Dunnett’s multiple comparisons, ONE-WAY ANOVA **p ≤ 0.01, ****p ≤ 0.0001) of four independent experiments performed in triplicates. ( |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Transendothelial migration of lymphoma cells. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | VAL cell migration through mLEC towards 10 nM CXCL12 was measured after 8h incubation. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Cell migration was calculated as percentage of the input (% migrated cells). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Cumulative data from three independent experiments measured in triplicates (means ± SD, Turkey’s multiple comparison ONE-WAY ANOVA ns (not significant), p≥0.05, ****p ≤ 0.0001). ( |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | (Left) ACKR3 (mAb 11G8) surface expression on VAL-wt cells before (upper panel, before) and after transendothelial migration (lower panel, after) towards 10 nM CXCL12 as in (C). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Representative plots from ten independent experiments performed in duplicates. ( |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Percentage of cells expressing ACKR3 on the plasma membrane before and after migration. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Cumulative data from five different experiments measured in triplicates (means ± SD, unpaired t-test, ****p ≤ 0.0001). ( |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Left side: flow cytometry plot showing ACKR3 (mAb 11G8) and CXCR5 (mAb J252D4) surface expression on VAL-wt (left panel). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Transendothelial migration of VAL-wt towards increasing concentrations of CXCL13 (0.1, 0.3 and 1 µM) (bar chart). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Right side: flow cytometry plot showing ACKR3 (mAb 11G8) and CXCR5 (mAb J252D4) surface expression on VAL-ko (left panel). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Transendothelial migration of VAL-ko through mLEC towards increasing concentrations of CXCL13 (0.1, 0.3 and 1 µM) (bar chart). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Cell migration was calculated as described above. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Bar charts show cumulative data of three independent experiments performed in triplicates (means ± SD, Dunnett’s multiple comparisons, ONE WAY ANOVA, **p ≤ 0.01, ***p ≤ 0.001). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | To assess the functionality of ACKR3 we took advantage of a previously developed specific chemokine uptake assay (42). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | CXCL11_12 AF647 is a fluorescent chimeric chemokine side-specific labeled at the C-terminus, composed of the N-terminus of CXCL11 and the main body of CXCL12. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | The chimera specifically binds ACKR3, but not CXCR3 or CXCR4, the respective cognate receptors for CXCL11 and CXCL12. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | VAL-wt and DOHH2 readily internalized the chimera ( Figure 1B ). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Hence, despite the limited surface expression of ACKR3 ( Figure 1A ), the receptor appears functional on both DLBCL lines. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | The observation is in agreement with the notion that the receptor cycles between the plasma membrane and endocytic compartments (6). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | As expected, VAL-ko did not scavenge the chimera and displayed low unspecific binding ( Figure 1B and Figure S1B ). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Chemokine scavenging and receptor internalization requires the intact C-terminus of ACKR3 (6). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | We reintroduced into VAL-ko ACKR3 with a truncated C-terminus by stable transfection resulting in VAL-ACKR3-ΔC cells (VAL-ACKR3-ΔC). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | VAL-ACKR3-ΔC poorly scavenged CXCL11_12 AF647 indicating that the C-terminus of ACKR3 is required for scavenging and receptor internalization ( Figures S1B, C ), consistent with previous findings (6, 43). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Next, we assessed the chemotactic response towards CXCL12. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Chemotaxis assays were performed as previously described with transwell plates coated with a monolayer of endothelial cells grown on a collagen-based extracellular matrix (32). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | The presence of endothelial cells optimizes the migration of lymphoma cells. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | VAL cells were allowed to migrate through a layer of mouse lymphatic endothelial cells (mLEC) for 8h in the absence and presence of an optimal concentration of CXCL12 (10 nM) in the lower compartment. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | In agreement with our previous findings (32), under these conditions about 20% of VAL-wt migrated into the lower compartment in the presence of chemokine, which accounts for a 3-fold increase compared to unstimulated chemokinesis. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | By contrast, VAL-ko, which express equal surface levels of CXCR4 showed no response to CXCL12, but also no spontaneous migration ( Figure 1C ). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | The observation was confirmed with genetically different clones to exclude off-target effects on cell migration through editing of ACKR3 by CRISPR/Cas9. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Chemokinesis of VAL cells through mLEC was not inhibited in the presence of the CXCR4 antagonist AMD3100, suggesting a basal migratory activity that was not mediated by CXCR4 ( Figure S1D ). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Similarly, VAL-ACKR3-ΔC, which express comparable CXCR4 levels on the surface ( Figure S1Ei ) did not perform CXCL12-dependent migration ( Figure S1Eii ). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | The observation suggests that the C-terminus is necessary for ACKR3 activity during VAL cell migration. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | We next compared the surface expression of ACKR3 on VAL-wt before and after migration towards CXCL12. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | The fraction of cells, which expressed ACKR3 at the plasma membrane increased from about 17% to 40-50% after chemotaxis ( Figure 1D ). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | The observation could indicate that cells, which express ACKR3 at the plasma membrane, migrate more efficiently. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | However, it cannot be excluded that cells upregulate surface expression of the receptor during migration. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | To get a better insight we sorted ACKR3 and ACKR3 VAL cells and analyzed their migratory properties in chemotaxis assays. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | The efficiency of cells expressing ACKR3 at the surface was notably higher compared to cells that did not present ACKR3 at the plasma membrane. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Moreover, VAL-wt lacking ACKR3 surface expression did not upregulate the receptor during migration ( Figure S1F ). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Nevertheless, in ACKR3 negative VAL-wt the mRNA of the receptor is not absent compared to the genetically modified VAL-ko (32). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Hence, it cannot be excluded that ACKR3 expressed on endosomal structures somehow contributes to the migration. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | All together, these findings suggest that functional ACKR3 plasma membrane expression is necessary to support efficiently CXCR4-dependent cell migration. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | In order to exclude a general inhibitory effect on VAL cell migration by ACKR3 deletion we examined the chemotaxis towards CXCL13, the ligand for CXCR5, which is expressed on both, VAL-wt and VAL-ko ( Figure 1E ). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | With increasing concentrations of CXCL13 we observed a typical bell-shaped migration response by both cell types ( Figure 1E ), indicating that VAL-ko retain the capability to sense a chemokine gradient, polarize and migrate. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | In addition, we explored the ability of VAL-wt and VAL-ko to migrate in response to stimulation of CCR7 with CCL19. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | VAL-wt, which heterogeneously express CCR7 ( Figure 1A ), were sorted for CCR7 surface expression and tested separately. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | CCR7 VAL-wt, which do not express ACKR3 on the surface ( Figure 1A ), migrated more efficiently than the CCR7 ACKR3 sorted cells ( Figure S1G ). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | The data indicate that the moderate chemotaxis towards CCL19 correlates with CCR7 surface expression. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | In line with this, VAL-ko cells, which do not express CCR7 ( Figure 1A ) did not migrate towards CCL19 ( Figure S1G ). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | The observation that VAL-wt, which do not express ACKR3 on the surface, can migrate towards CXCL12 in the presence of cells exposing the receptor on the plasma membrane was intriguing ( Figure 1D ). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Previous data showed that in zebrafish ACKR3 expressed in trans on stromal cells can support the CXCL12-mediated migration of primordial germ cells (44). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | It is plausible that ACKR3 positive VAL-wt, when locally scavenging CXCL12, shape micro-gradients that are sensed by CXCR4 VAL cells that do not express ACKR3 on the surface. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | The hypothesis implies that ACKR3 scavenging activity is necessary for VAL cell migration. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | To address the assumption, we used mLEC transwell assays to measure CXCL12-induced chemotaxis of VAL-ko in the presence of VAL-wt. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | We mixed VAL-wt and CFP VAL-ko in a 1:1 ratio, which enables the identification of the two cell types by flow cytometry. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | The mixture was allowed to migrate towards different concentrations of CXCL12 ( Figure 2A ). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | CFP VAL-ko in the 1:1 mixture with VAL-wt showed a typical bell-shaped migratory response towards CXCL12, whereas VAL-ko cells alone poorly responded ( Figure 2A ). |
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