PMCID string | Title string | Sentences string |
|---|---|---|
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Moreover, in the mixture, the CFP VAL-ko cells migrated with a similar efficiency as VAL-wt cells ( Figures 2A, B ). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Next, we addressed the role of the C-terminus of ACKR3 in promoting the migration of VAL-ko. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | VAL-ACKR3-ΔC, barely supported VAL-ko migration towards CXCL12 in a 1:1 mixture, highlighting the importance the C-terminus for scavenging ( Figure S1C ), migration ( Figure S1Eii ) and stimulation in trans ( Figure 2B ). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | It is conceivable that the scavenging activity is essential for chemotaxis of ACKR3 expressing cells and to support migration of VAL-ko, however it cannot be excluded that the C-terminus mediates additional intracellular signaling unrelated to receptor trafficking. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | The later assumption is in line with previous findings (9) where it was shown that phosphorylation-deficient (C-terminus) ACKR3 does not scavenge chemokines but rescues the lethal phenotype of receptor-deficient mice. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | VAL-wt cells induce the migration of VAL-ko cells. ( |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Transendothelial migration of VAL cells (as in Figure 1 ) towards different concentrations of CXCL12 (1, 10, 30 nM). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Cyan symbols and cyan lines (VAL-ko) displays % migrated VAL-ko in the absence of VAL-wt. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | The % migrated VAL-ko (gated on CFP) in a 1:1 mixture with VAL-wt was calculated from the input of VAL-ko in the mixture (VAL-ko mixed, cyan filled symbols and black lines). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Black symbols: % migrated VAL-wt calculated from the respective input. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Calculation by flow cytometry as in Figure 1 . |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Cumulative data of three independent experiments measured in triplicates (means ± SD, Dunn’s multiple comparisons ONE WAY ANOVA, *p ≤ 0.05, ***p ≤ 0.001) (B) Transendothelial migration of VAL cells towards 10 nM CXCL12 or medium. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | VAL-ko were mixed 1:1 with VAL-wt (dark cyan) or VAL-ΔC (green) and the % migrated VAL-ko was calculated from the input of VAL-ko in the mixture. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Quantification was performed as described in Figure 1 . |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Cumulative data of three independent experiments measured in triplicates (means ± SD, Turkey’s multiple comparison, ONE WAY ANOVA, ***p ≤ 0.001). ( |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Migration of DOHH2 cells. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | DOHH2 cells were mixed 1:1 with VAL-ko and the mixture allowed to migrate for 8 h towards 10 nM CXCL12 or medium. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | The % migrated DOHH2 (grey bars) and of VAL-ko (cyan bars) were calculated from the respective inputs in the mixture. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Experiments performed in triplicates, representative example of three independent experiments (means ± SD, Turkey’s multiple comparison, ONE WAY ANOVA ***p ≤ 0.001). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | To extend the observation of DLBCL migration we measured mLEC transwell chemotaxis of DOHH2 cells in response to CXCL12. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | DOHH2 cells migrated more efficiently than VAL-wt, but also displayed enhanced chemokinesis. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | When DOHH2 cells were mixed with VAL-ko cells they induced chemokinesis of VAL-ko cells and barely supported chemotaxis towards CXCL12 ( Figure 2C ). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Taken together, the data suggest that expression of full-length ACKR3 on leader cells is needed to induce the CXCL12-dependent cell-to-cell-induced migration of CXCR4 VAL-ko. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | We used a previously reported localized tumor xenograft model in NOD/SCID mice (32) to investigate lymphoma cell migration in vivo. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | We injected 10 lymphoma cells subcutaneously in the flanks of NOD/SCID mice. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | All animals showed a comparable increase in body weight and tumor size ( Figure 2SA ). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | After 20-21 days, animals were sacrificed and the mass of the primary tumor was measured. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | No significant differences in mass were observed between tumors grown from wild type DLBCL, VAL-wt cells and DOHH2, VAL-ko and the respective mixtures of wild type and VAL-ko ( Figure 3A ). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | NOD/SCID mice barely developed sizable lymph nodes due to the lack of endogenous lymphocytes. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Injection of wild type DLBCL cells led to measurable mass of the draining lymph node. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | By contrast, the draining lymph nodes of tumors from VAL-ko remained hardly detectable ( Figure 3A ). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | However, an increase in lymph node mass was observed, when 1:1 mixtures of wild type DLBCL and VAL-ko were injected ( Figure 3A ). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | To test whether under these conditions VAL-ko contributed to the increase in mass of the draining lymph node, we used flow cytometry to measure the presence of CFP VAL-ko. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | While VAL-ko alone did not migrate to the axillary lymph node, in the presence of VAL-wt or DOHH2 the CFP VAL-ko could readily be detected ( Figure 3B ). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Hence, like in vitro, also in vivo wild type lymphoma cells appeared to promote the migration of ACKR3 deficient VAL-ko. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | In the mixture preferentially ACKR3 positive VAL-wt migrated to the draining lymph node along with VAL-wt, which do not express ACKR3 at the surface and CFP VAL-ko ( Figure 3C ). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Consistent with our in vitro observations ( Figure 1D ) the proportion of VAL-wt expressing ACKR3 on the surface was markedly increased from 18% to over 50% in the draining lymph node. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | By contrast, the expression of CCR7 was unaltered on VAL-wt and remained essentially absent on CFP VAL-ko, suggesting that the receptor may not contribute to draining lymph node infiltration ( Figure S2B ). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Migration of VAL-ko from the primary tumor to the draining lymph node is enhanced in the presence of ACKR3 expressing cells. ( |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Tumor (left) and lymph node (right) weights from NOD/SCID common γ-chain mice injected with 10 VAL-wt, VAL-ko and DOHH2 cells alone and as 1:1 mixture VAL-wt:VAL-ko and DOHH2:VAL-ko. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Weights are reported as means ± SD from three independent xenograft experiments with 4-5 animals per group. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Tumor and lymph node t-test single comparison: ns, p≥0.05, *p≤ 0.05, **p ≤ 0.01. ( |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Total number of CFP VAL-ko present in the draining axillary lymph node from the same experiments. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Lymph node cells were analyzed by flow cytometry and gated for hCD19 (HIB19 or SJ25C1), mCD45 (30-F11) and CFP expression (means ± SD, t-test single comparison, ns, p≥0.05 **P ≤ 0.01). ( |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Surface expression of ACKR3 on VAL-wt cells and CFP expression in VAL-ko extracted from a representative localized tumor (upper panel) and from the corresponding lymph node (lower panel). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Representative data from one experiment shown in A (n= 4-5). ( |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Confocal images of sections of a tumor generated by injecting a 1:1 mixture of VAL-wt and VAL-ko (CFP). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Tumors were fixed for 48h in a solution of 4% paraformaldehyde and Vibratome sections stained overnight with anti-hCD19 (mAb HIB19) anti-mPDPN (mAb 8.1.1) and anti-mCD31 (mAb MEC13.3). ( |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Confocal images of sections of a draining lymph node from a tumor generated by injecting a 1:1 mixture of VAL-wt and VAL-ko (CFP). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Lymph nodes were fixed for 5h in a solution 4% paraformaldehyde and Vibratome sections were stained overnight with anti-hCD19 Ab (mAb HIB19), anti-mPDPN (mAb 8.1.1). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Immunofluorescence (IF) analysis of sections from tumors of VAL-wt:VAL-ko mixtures by confocal microscopy revealed that VAL-wt and VAL-ko are randomly distributed in the tumor mass. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Using podoplanin (PDPN) and CD31 staining for mouse lymphatic and endothelial vessels we found a similar localization for both cell populations ( Figure 3D ). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | By contrast, IF analysis of axillary lymph node sections from mice bearing VAL-wt:Val-ko tumors revealed striking differences in the distribution of the two cell populations. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Human CD19 VAL-wt almost completely populated the entire draining lymph node. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | By contrast, CFP VAL-ko were found at the edge of the lymph node, close to the sub-capsular sinus in clusters surrounded by VAL-wt cells ( Figure 3E ). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Taken together, the data indicate that like in vitro lymphoma cells can also promote the migration of VAL-ko in vivo. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | To investigate further the migration and the cooperation between cells, we used a 3D migration and quantitative computational (45) analysis system. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Cells were embedded in a collagen matrix and chemotaxis towards CXCL12 was followed by time-lapse imaging ( Figure 4A ). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Tracks of migrating cells were generated automatically by computational analysis and used to extrapolate data of statistical significance to calculate displacement, track length and velocity of single cells. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Single cell data were pooled into experimental groups for comparison ( Figure 4B ). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | The analysis confirmed that VAL-ko are unable to migrate towards CXCL12 ( Figure S3A ) while the mixture of migrating VAL-ko:VAL-wt is mobile and migration competent ( Figure S3B ). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Displacement and track length of VAL-ko in the mixture is comparable to that of VAL-wt ( Figure 4B ). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | However, cells in the mixture appeared to migrate with an intermediate velocity being faster than VAL-ko cells alone, but slower than VAL-wt cells ( Figure 4B ). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Similarly, plotting the tracks on common origin revealed that (i) VAL-wt in the mixture are highly motile, (ii) VAL-ko essentially do not move, while (iii) the migratory capacity of VAL-ko is partially restored in the presence of VAL-wt ( Figure 4C ). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | The results are consistent with the transwell assays and the in vivo data, demonstrating that the presence of ACKR3 is essential to promote migration in cis and in trans. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | CXCL12 stimulated VAL-wt increase the 3D motility and directional migration of VAL-ko. ( |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Schematic representation of 3D migration chamber showing a chemotactic gradient (CXCL12 diffusion) from left to right. ( |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Violin plots showing displacement, length and velocity of VAL-ko alone (light cyan), VAL-ko in a 1:1 mixture with VAL-wt (VAL-ko mixed, dark cyan) and VAL-wt in the same mixture (VAL-wt mixed, grey). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Tracking analyses were performed using Imaris software (means, Turkey’s multiple comparisons test, ONE-WAY ANOVA ns, p≥0.05, ****p ≤ 0.0001). ( |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Plots of tracks with a common origin. ( |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | VAL-wt mixed, (ii) VAL-ko alone, (iii) VAL-ko mixed. ( |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Scatter plots of directionality vs arrest coefficients of 1000 VAL-wt mixed, VAL-ko alone, VAL-ko mixed. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Gates with differently colored dots indicate four different motility patterns. ( |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Violin plots of changes in velocity of VAL-ko and VAL-wt, relative to the number of motile (0, 1, 2) VAL-wt in a 50 µm radius (means, Mann-Whitney t-test ns, p≥0.05, ****p ≤ 0.0001). ( |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Directionality changes over time of a VAL-ko (red thick line) with respect to directionality changes of two VAL-wt in a 50 µm radius (orange and red thin lines, upper plot). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | The lower plot shows the same directionality changes of a single VAL-ko (red thick line), compared to the average of directionality value of VAL cells in the 50 µm radius. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | To better characterize differences in motility, we analyzed the behavior of individual cells over time. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | We applied an algorithm using mobility values to generate plots that distinguish four populations according to their migratory behavior. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | We quantified instantaneous motility measures over time, by dividing each track into fragments (tracklets), and performed a tracklet-based action analysis as previously described (46). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | From the motility measures, we computed the continuous arrest coefficient (46), that is the proportion of time during which a cell does not move. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Cells with low motility are associated with high values of arrest coefficient. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Moreover, we computed the instantaneous directionality (46), which was associated with high values for polarized cells migrating along straight trajectories. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | We assigned these coefficients to 1000 tracklets of each group: VAL-wt and VAL-ko in the mixture (separately analyzing CFP and CFP cells) and VAL-ko alone ( Figure 4D ). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | For VAL-wt, in a 1:1 mixture with VAL-ko, 233 tracklets displayed low arrest coefficients and low directionality, which indicates that these cells perform chemokinesis (green gate), whereas 511 tracklets were associated with immobile cells, characterized by tracklets with a high arrest coefficient and low directionality (blue gate). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Tracklets of cells, which protruded lamellipods, hence visibly polarized, but showed slow or no migration (red gate 58 tracklets), were defined by a high arrest coefficient and high directionality (deduced from the polarity). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Finally, 198 tracklets (orange gate) displayed low arrest coefficients and high directionality and were associated with cells that performed a pronounced directional migration. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | VAL-ko when placed alone in the chamber were found to be mostly immobile (956 tracklets in the blue gate). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | However, VAL-ko in the mixture displayed similar motility as VAL-wt with slightly less directional migration ability (103 vs. 198 tracklets). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Our algorithm applied to a large number of tracklets confirmed the motility of VAL-wt and their ability to promote the migration of VAL-ko. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | We further analyzed whether the velocity of VAL-ko and VAL-wt migration depends on a motile VAL-wt in the direct neighborhood. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Figure 4E shows that a VAL-ko in the presence of at least one motile VAL-wt within a radius of 50 µm migrated with significantly higher velocity compared to VAL-ko where no motile VAL-wt were in close proximity. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | We observed that the increase in velocity of migration of VAL-ko was similar whether one or two motile VAL-wt were in the neighborhood, suggesting no additive effect. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | The same analysis performed for the velocity of VAL-wt revealed that the motility of the cells was also influenced by the presence of a motile VAL-wt within a radius of 50 µm. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | The finding suggested that VAL-ko and VAL-wt might perform a secondary migration, which could be triggered either by microgradients of CXCL12 created by ACKR3 VAL-wt or by another stimulus that is released during the migration of VAL-wt along a CXCL12 gradient. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | By analyzing in depth the tracks of VAL-ko we saw that the cells often migrate to a spot where a VAL-wt had briefly paused and left (Movies S1-3). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | In addition, we measured the changes in directionality of VAL-ko and VAL-wt in close proximity and plotted the data over time ( Figure 4F ). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | We found that the changes in directionality of VAL-ko were in most cases preceded by a change in VAL-wt directionality ( Figure 4F upper panel). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Moreover, the migration of a VAL-ko was similar to the overall movement of motile cells in a radius of 50 µm ( Figure 4F , lower panel). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | The observations support the assumption that the migration of VAL-ko depends on the movement of VAL-wt, in line with the hypothesis that DLBCL invade tissues through cell-to-cell-induced migration as a heterogeneous population of cells. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Pertussis toxin (PTX) treatment inhibits the transmigration of VAL-wt towards CXCL12 but has no effect on the VAL cell chemokinesis ( Figure S4A ). |
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