L‐Selectin Expression is Influenced by Phosphatase Activity in Chronic Lymphocytic Leukemia

Debreceni, Ildikó Bekéné; Szász, Róbert; Kónya, Zoltán; Erdõdi, Ferenc; Kiss, Flóra; Kappelmayer, János

doi:10.1002/cyto.b.21771

Cited by 7 publications

(5 citation statements)

References 29 publications

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“…For instance, E-selectin has been shown to be a key receptor in leukemia [ 24 , 25 ], myeloma [ 23 ], as well as in solid tumors such as pancreatic [ 26 , 27 , 28 ], prostate [ 29 , 30 ], colon [ 31 , 32 ] and breast [ 33 , 34 , 35 ] cancer cells. L-selectin has been shown to be a key receptor for chronic lymphocytic leukemia [ 20 , 36 ]. Moreover, P-selectin has been shown to play an important role in myeloma [ 15 , 18 , 22 , 23 ].…”

Section: The Role Of E-selectin In Cancer Pathophysiologymentioning

confidence: 99%

Targeting E-selectin to Tackle Cancer Using Uproleselan

Muz

Abdelghafer

Markovic

et al. 2021

Cancers

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E-selectin is a vascular adhesion molecule expressed mainly on endothelium, and its primary role is to facilitate leukocyte cell trafficking by recognizing ligand surface proteins. E-selectin gained a new role since it was demonstrated to be involved in cancer cell trafficking, stem-like properties and therapy resistance. Therefore, being expressed in the tumor microenvironment, E-selectin can potentially be used to eradicate cancer. Uproleselan (also known as GMI-1271), a specific E-selectin antagonist, has been tested on leukemia, myeloma, pancreatic, colon and breast cancer cells, most of which involve the bone marrow as a primary or as a metastatic tumor site. This novel therapy disrupts the tumor microenvironment by affecting the two main steps of metastasis—extravasation and adhesion—thus blocking E-selectin reduces tumor dissemination. Additionally, uproleselan mobilized cancer cells from the protective vascular niche into the circulation, making them more susceptible to chemotherapy. Several preclinical and clinical studies summarized herein demonstrate that uproleselan has favorable safety and pharmacokinetics and is a tumor microenvironment-disrupting agent that improves the efficacy of chemotherapy, reduces side effects such as neutropenia, intestinal mucositis and infections, and extends overall survival. This review highlights the critical contribution of E-selectin and its specific antagonist, uproleselan, in the regulation of cancer growth, dissemination, and drug resistance in the context of the bone marrow microenvironment.

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Section: The Role Of E-selectin In Cancer Pathophysiologymentioning

confidence: 99%

Targeting E-selectin to Tackle Cancer Using Uproleselan

Muz

Abdelghafer

Markovic

et al. 2021

Cancers

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“…Peripheral blood neutrophils were homogeneous and express FcγRIII (CD16) and L-selectin (CD62L) within a narrow range, typically characterized as CD16 bright CD62L bright (mature), CD16 dim CD62L bright (immature), CD16 dim CD62L dim (apoptotic) neutrophils ( 22 ). L-selectin(CD62L) can account for impaired rolling and migration ability of leukocytes ( 23 ). The expression of HLA-DR was defined as an activation marker ( 24 ).…”

Section: Resultsmentioning

confidence: 99%

The peripheral and decidual immune cell profiles in women with recurrent pregnancy loss

Qin

Xu²,

Chen³

et al. 2022

Front. Immunol.

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Recurrent pregnancy loss (RPL) affects 1-2% of couples of reproductive age. Immunological analysis of the immune status in RPL patients might contribute to the diagnosis and treatment of RPL. However, the exact immune cell composition in RPL patients is still unclear. Here, we used flow cytometry to investigate the immune cell profiles of peripheral blood and decidual tissue of women who experienced RPL. We divided peripheral immune cells into 14 major subgroups, and the percentages of T, natural killer T (NKT)-like and B cells in peripheral blood were increased in RPL patients. The decidual immune cells were classified into 14 major subpopulations and the percentages of decidual T, NKT-like cells and CD11chi Mφ were increased, while those of CD56hi decidual NK cells and CD11clo Mφ were decreased in RPL patients. The spearmen correlation analysis showed that the proportion of peripheral and decidual immune cells did not show significant correlations with occurrences of previous miscarriages. By using flow cytometry, we depicted the global peripheral and decidual immune landscape in RPL patients. The abnormalities of peripheral and decidual immune cells may be involved in RPL, but the correlations with the number of previous miscarriages need further verification.

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“…The protein tyrosine phosphatase receptor (PTPR) type O Tyr-phosphatase was shown to interfere with CLL progression and survival and was proposed as a tumor suppressor gene (17). Moreover, it was reported that PHLPP1 and phosphatase-2A Ser/Thr-phosphatases are downmodulated in CLL, thus favoring prosurvival signals in CLL (18,19). Moreover, SHIP1 and SHIP2 5-phosphate phosphatases have been shown to interfere with prosurvival signaling mechanisms in CLL (20,21).…”

Section: Activation Of Protein Tyrosine Phosphatase Receptor Type G S...mentioning

confidence: 99%

Activation of Protein Tyrosine Phosphatase Receptor Type γ Suppresses Mechanisms of Adhesion and Survival in Chronic Lymphocytic Leukemia Cells

Montresor

Toffali

Fumagalli

et al. 2021

The Journal of Immunology

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The regulatory role of protein tyrosine kinases in β1- and β2-integrin activation and in the survival of chronic lymphocytic leukemia (CLL) cells is well established. In contrast, the involvement of protein tyrosine phosphatases in CLL biology was less investigated. We show that selective activation of the protein tyrosine phosphatase receptor type γ (PTPRG) strongly suppresses integrin activation and survival in leukemic B cells isolated from patients with CLL. Activation of PTPRG specifically inhibits CXCR4- as well as BCR-induced triggering of LFA-1 and VLA-4 integrins and mediated rapid adhesion. Triggering of LFA-1 affinity is also prevented by PTPRG activity. Analysis of signaling mechanisms shows that activation of PTPRG blocks chemokine-induced triggering of JAK2 and Bruton’s tyrosine kinase protein tyrosine kinases and of the small GTP-binding protein RhoA. Furthermore, activated PTPRG triggers rapid and robust caspase-3/7–mediated apoptosis in CLL cells in a manner quantitatively comparable to the Bruton’s tyrosine kinase inhibitor ibrutinib. However, in contrast to ibrutinib, PTPRG-triggered apoptosis is insensitive to prosurvival signals generated by CXCR4 and BCR signaling. Importantly, PTPRG activation does not trigger apoptosis in healthy B lymphocytes. The data show that activated PTPRG inhibits, at once, the signaling pathways controlling adhesion and survival of CLL cells, thus emerging as a negative regulator of CLL pathogenesis. These findings suggest that pharmacological potentiation of PTPRG tyrosine-phosphatase enzymatic activity could represent a novel approach to CLL treatment.

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L‐Selectin Expression is Influenced by Phosphatase Activity in Chronic Lymphocytic Leukemia

Cited by 7 publications

References 29 publications

Targeting E-selectin to Tackle Cancer Using Uproleselan

Targeting E-selectin to Tackle Cancer Using Uproleselan

The peripheral and decidual immune cell profiles in women with recurrent pregnancy loss

Activation of Protein Tyrosine Phosphatase Receptor Type γ Suppresses Mechanisms of Adhesion and Survival in Chronic Lymphocytic Leukemia Cells

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