PMCID string | Title string | Sentences string |
|---|---|---|
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Groups of six mice were then treated with either 20mg/kg alisertib, 30mg/kg Aurkin A, 20mg/kg alisertib + 30mg/kg Aurkin A combination, or a vehicle control (DMSO volume match). |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Mice were given the corresponding treatment once a day for five days a week. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | After two weeks, treatment was then withheld for a week, followed by another five-day-a-week treatment cycle. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | One mouse in the combination group died fifteen days into the treatment with no additional mortality events seen in any other mouse groups. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Mouse groups were sacrificed on day 24 as alisertib and control groups were approaching the approved protocol's max tumor size of 2cm. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | A statistically significant difference was found between the combination group and the control (p=0.0153), alisertib (p=0.027), and Aurkin A (p=0.0323) groups. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Mouse tumors were then harvested, formalin-fixed, and hematoxylin and eosin stained. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Cells were then classified as polyploid or normalploid based nucleus to cell area ratio, using the QuPath Bioimaging Analysis software (Fig. 7a and b). |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Ploidy analysis from the vehicle control 84.3% normalploid and 15.7% polyploid respectively (Fig. 7c). |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Aurkin A treatment showed 83.8% normalploid and 16.2% polyploid cells respectively. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | The alisertib treated group showed a significant increase in polyploidy to 43.6% and decrease in normaloid cells to 56.7%. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | In contrast, Aurkin A plus alisertib reduced polyploidy to levels seen in the control to 16.1% with 83.9% normalploid cells. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Fig. 7Alisertib Induced Polyploidy is Significantly Disrupted by Aurkin A in A VAL Mouse Xenograft Model. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Alisertib induced polyploidy is significantly disrupted by Aurkin A in a VAL mouse xenograft model. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | SCID mice were injected with 1 × 106 VAL cells in sterile saline subcutaneously in the left flank. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Mice were pair matched based on tumor volume three weeks post injection and grouped into an alisertib 20mg/kg, Aurkin A 30mg/kg, Alisertib 20mg/kg + Aurkin A 30mg/kg combination, and vehicle control (DMSO volume match) groups. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Mice were given the corresponding treatment once a day for five days a week. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Treatment was then withheld for two weeks followed by another five-day-a-week treatment cycle. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | One mouse in the combination group died 15 days after the start of treatment. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Tumor volume was normalized to the volume at the start of treatment and graphed. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | There was a statistically significant difference in tumor volume between the combination group and the control (p=0.0153), alisertib (p=0.027), and Aurkin A (p=0.0323) groups (A). |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Tumors dissected and fixed in formalin and paraffin embedded. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Slides were H&E stained and QuPath Bioimaging Analysis software performed for nucleus to cell ratio to identify polyploidy cells (B). |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | depicts H&E stain from a vehicle control treated mouse. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | The ploidy classification performed by QuPath highlights normalploid cells in green and polyploid cells in blue (C). |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Three different fields of at least 10,000 cells were counted for each condition (D).Fig 7 Alisertib Induced Polyploidy is Significantly Disrupted by Aurkin A in A VAL Mouse Xenograft Model. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Alisertib induced polyploidy is significantly disrupted by Aurkin A in a VAL mouse xenograft model. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | SCID mice were injected with 1 × 106 VAL cells in sterile saline subcutaneously in the left flank. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Mice were pair matched based on tumor volume three weeks post injection and grouped into an alisertib 20mg/kg, Aurkin A 30mg/kg, Alisertib 20mg/kg + Aurkin A 30mg/kg combination, and vehicle control (DMSO volume match) groups. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Mice were given the corresponding treatment once a day for five days a week. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Treatment was then withheld for two weeks followed by another five-day-a-week treatment cycle. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | One mouse in the combination group died 15 days after the start of treatment. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Tumor volume was normalized to the volume at the start of treatment and graphed. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | There was a statistically significant difference in tumor volume between the combination group and the control (p=0.0153), alisertib (p=0.027), and Aurkin A (p=0.0323) groups (A). |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Tumors dissected and fixed in formalin and paraffin embedded. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Slides were H&E stained and QuPath Bioimaging Analysis software performed for nucleus to cell ratio to identify polyploidy cells (B). |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | depicts H&E stain from a vehicle control treated mouse. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | The ploidy classification performed by QuPath highlights normalploid cells in green and polyploid cells in blue (C). |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Three different fields of at least 10,000 cells were counted for each condition (D). |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Alisertib is an ATP site inhibitor of AK-A, a key regulatory mitotic kinase. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | We characterize cell cycle disruption and resulting polyploidy from alisertib treatment in DLBCL U2932 and VAL cell lines. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Increasing concentrations of alisertib up to 1µM (clinically achieved) displayed increased 4n, 8n, and 16n polyploid cells along with decreased G1 cell populations. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Cells treated with alisertib have a drastically altered morphology, significantly larger and amorphic. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Alisertib treatment of FUCCI U2932 cells shows that one third of all treated cells can generate polyploidy via endomitosis, increasing longevity and resistance to apoptosis. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Additionally, alisertib treatment induces an aggressive growth phenotype, as they can undergo G1 cell cycle slippage, thus shortening the overall cell cycle. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | The VAL mouse xenograft model further evidences this accelerated growth phenotype and longevity of polyploid cells, as alisertib treated tumors had a significantly higher growth rate when compared to the DMSO control treatment. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Aurkin A, a small molecule inhibitor, prevents allosteric binding of TPX2 to the N-terminal kinase domain of AK-A and sensitizes U2932 cells to alisertib. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | This is evidenced as there was a decrease in alisertib IC50 from 983nM to 34nM with the addition of 100µM Aurkin A. MDA-MB-231, Hela, Mia PaCa-2, U-2 OS, Granta-519 cell lines also saw a significant drop in IC50 with the addition of 100µM Aurkin A. Calculated combination indexes show that the combination of alisertib and Aurkin A is synergistic. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | This provides evidence that lower concentrations of alisertib can be used with Aurkin A combination to kill a cell population. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | The addition of Aurkin A to alisertib significantly increased the level of apoptosis in U2932 cells, as 500nM alisertib alone had a viable cell population of 67% which declined to 12% with the addition of 100µM Aurkin A. The combination of Aurkin A plus alisertib inhibits cell cycle slippage and endomitotic activity of alisertib resulting in decreased polyploidy and increased apoptosis. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | An in vivo VAL xenograft mouse model confirmed these results as there was a significant reduction in tumor growth between the combination and other treatment groups. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Additionally, significantly less polyploidy was observed between alisertib treatment (43.6%) and in combination alisertib plus Aurkin A treatment (16.1%). |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Interestingly, results from the MTS assays suggest synergy from the combination of alisertib and Aurkin A is not isolated to just DLBCL cell lines. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | However, further testing is required to validate this hypothesis. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | While the mechanism by which alisertib and Aurkin A synergy yet to be fully identified, we hypothesize that the dual inhibition of AK-A by alisertib and Aurkin A results in cell cycle arrest in late G2 or early M, resulting in eventual cell death. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Results from the FUCCI experiments strengthen this hypothesis as approximately 90% of cells treated with the combination therapy were unable to progress past G2/M resulting in cell cycle arrest and eventual cell death. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | However, 10% combination cells failed to progress to through G1, leading to cell cycle arrest and cell death. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | This phenotype could still be explained by the AK-A dual inhibition hypothesis, as it is possible that cell undergoing mitosis at the time of treatment may have experienced significant DNA damage, or chromosomal mis-segregation due to AK-A/AK-B inhibition. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | This DNA damage could prevent progression through the S phase DNA damage checkpoint and lead to cell death. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | A phase II clinical trial of alisertib conducted in 48 patients with aggressive B- and T- cell NHL described the safety, toxicity profile and maximum tolerated dose (MTD) . |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Pharmacokinetic analysis of alisertib showed a mean effective dose to be 2.375µM, however, the MTD was established at 1.504µM . |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | The sensitization of alisertib with Aurkin A in complete AK-A inhibition is of high clinical importance as the alisertib dose can be reduced by 3-fold not only to prevent polyploidy, enhance efficacy but significantly reduce toxicity to normal tissue. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Apoptosis data in U2932 cells shows a viable cell population of 39% after five days of 5µM alisertib treatment, which declined to 22% after four days without treatment. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | At 500nM alisertib a five-day viable population of 67% improved to 82% after four days without treatment. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | However, addition of 100µM Aurkin A to 500nM alisertib produced a viable population of 12% which increased to 19% post treatment. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | This change in viable populations strongly suggests that Aurkin A significantly sensitizes U2932 and VAL cells to alisertib, more than 10-fold of alisertib alone. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | In addition, it potentiates killing of polyploid cells, which could help limit cancer recurrence. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | This Aurkin A effect warrants further investigation in other cancer cell types and with chemotherapeutic agents that induced drug-resistant polyploidy. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | This research was supported by R21ES035997 from NIEHS to E. Dray. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | The Mays Cancer Center (MCC) is supported by a grant from the National Cancer Institute (P30CA054174; Sung, P.). |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | The Flow Cytometry Shared Resource at UT Health San Antonio is supported by grants from the Cancer Prevention and Research Institute of Texas (RP210126; Berton, M.T.) and from the National Institutes of Health (S10OD030432; Berton, M.T.), and support from the MCC and the Office of the Vice President for Research at UT Health San Antonio. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Patrick J. Conway: Writing – original draft, Validation, Methodology, Investigation, Formal analysis, Data curation. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Bárbara De La Peña Avalos: Investigation, Data curation. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Jonathan Dao: Investigation, Data curation. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Sebastian Montagnino: Investigation, Data curation. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Dmytro Kovalskyy: Visualization, Software. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Eloise Dray: Writing – review & editing, Validation, Supervision, Resources, Project administration, Methodology, Conceptualization. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | Daruka Mahadevan: Writing – review & editing, Validation, Supervision, Resources, Project administration, Methodology, Conceptualization. |
PMC11225860 | Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma | The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Chemotaxis is an essential physiological process, often harnessed by tumors for metastasis. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | CXCR4, its ligand CXCL12 and the atypical receptor ACKR3 are overexpressed in many human cancers. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Interfering with this axis by ACKR3 deletion impairs lymphoma cell migration towards CXCL12. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Here, we propose a model of how ACKR3 controls the migration of the diffused large B-cell lymphoma VAL cells in vitro and in vivo in response to CXCL12. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | VAL cells expressing full-length ACKR3, but not a truncated version missing the C-terminus, can support the migration of VAL cells lacking ACKR3 (VAL-ko) when allowed to migrate together. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | This migration of VAL-ko cells is pertussis toxin-sensitive suggesting the involvement of a Gi-protein coupled receptor. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | RNAseq analysis indicate the expression of chemotaxis-mediating LTB4 receptors in VAL cells. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | We found that LTB4 acts synergistically with CXCL12 in stimulating the migration of VAL cells. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Pharmacologic or genetic inhibition of BLT1R markedly reduces chemotaxis towards CXCL12 suggesting that LTB4 enhances in a contact-independent manner the migration of lymphoma cells. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | The results unveil a novel mechanism of cell-to-cell-induced migration of lymphoma. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Cell migration is a widely conserved biological process, but the involved intracellular pathways are poorly understood. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Directional migration or chemotaxis is orchestrated by distinct cell surface receptors, which guide cells along gradients of increasing concentrations of attractants (1). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Chemokines, which constitute the largest family of chemoattractants, share a basic isoelectric point that allows them to be presented on cell surfaces and extracellular matrices (2, 3). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | They induce chemotaxis by binding to cognate G-protein-coupled receptors (GPCRs), which upon ligand binding activate via pertussis toxin-sensitive G proteins downstream pathways leading to cell migration (4, 5). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | In addition to conventional G-protein coupled chemokine receptors, chemokines bind to seven-transmembrane domain receptors, which do not activate G-proteins, called atypical chemokine receptors (ACKR) (3–5). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | ACKR3 acts mainly as a decoy with high affinity for the chemokine CXCL12 and with lower affinity for CXCL11, which are also ligands for the conventional receptors CXCR4 and CXCR3, respectively (6, 7). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | The physiological importance of the CXCL12/ACKR3/CXCR4 axis is underlined by the fact that absence of either component causes perinatal death in mice severely disrupting central nervous system and heart development (8–11). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Chemotaxis is governed by a chemokine-producing source, often constituted by stromal cells, and a juxtaposed sink that removes chemokines, either cells that express ACKRs or other mechanisms of degradation. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Removal of chemoattractants is essential to maintain gradients and to avoid blurring of the source. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Chemokine gradients are established over a relatively short distance of about 100 to 150 µm (12). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Therefore, chemotaxis is not involved in long distance cell displacements as observed in passive blood-flow mediated cell movement (13). |
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