Oncogenic Deregulation of Cell Adhesion Molecules in Leukemia

Windisch, Roland; Pirschtat, Nina; Kellner, Christian; Chen-Wichmann, Linping; Lausen, Jörn; Humpe, Andreas; Krause, Daniela; Wichmann, Christian

doi:10.3390/cancers11030311

Cited by 32 publications

(25 citation statements)

References 124 publications

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“…The mechanisms by which leukemic blast mobilization from and homing to the bone marrow occurs remain incompletely defined. HSCs express and interact with bone marrow stromal cells via various cell adhesion molecules that belong to the integrin receptor superfamily such as VLA-4, VLA-5, and LFA-1 which act as receptors for fibronectin and intracellular adhesion molecule-1 (ICAM-1) [ 42 , 43 ]. Other essential means of interaction between AML blasts and stromal cells are via CXCL12, CD44, selectins, and cadherins [ 43 ].…”

Section: The Bone Marrow Niche Under Physiologic Conditions and Itmentioning

confidence: 99%

“…Similarly, targeting CD44 and the CXCL12/CXCR4 axis has been shown in preclinical studies to eliminate leukemic stem cells and to increase the sensitivity to chemotherapy [ 45 , 46 ]. While inhibition of adhesion molecules such as VLA-4, CXCR4, and PSGL-1 can be used to increase the yield of CD34 + HSCs during leukapheresis for stem cell transplantation, VLA-4 could also play a role in chemotherapy resistance and LSC survival [ 42 , 47 ]. The interaction between VLA-4 and VCAM-1 protects leukemic blasts from apoptosis and has been linked to minimal residual disease and eventual disease relapse [ 48 ].…”

Section: The Bone Marrow Niche Under Physiologic Conditions and Itmentioning

confidence: 99%

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Hyperleukocytosis and Leukostasis in Acute Myeloid Leukemia: Can a Better Understanding of the Underlying Molecular Pathophysiology Lead to Novel Treatments?

Bewersdorf

Zeidan

2020

Cells

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Up to 18% of patients with acute myeloid leukemia (AML) present with a white blood cell (WBC) count of greater than 100,000/µL, a condition that is frequently referred to as hyperleukocytosis. Hyperleukocytosis has been associated with an adverse prognosis and a higher incidence of life-threatening complications such as leukostasis, disseminated intravascular coagulation (DIC), and tumor lysis syndrome (TLS). The molecular processes underlying hyperleukocytosis have not been fully elucidated yet. However, the interactions between leukemic blasts and endothelial cells leading to leukostasis and DIC as well as the processes in the bone marrow microenvironment leading to the massive entry of leukemic blasts into the peripheral blood are becoming increasingly understood. Leukemic blasts interact with endothelial cells via cell adhesion molecules such as various members of the selectin family which are upregulated via inflammatory cytokines released by leukemic blasts. Besides their role in the development of leukostasis, cell adhesion molecules have also been implicated in leukemic stem cell survival and chemotherapy resistance and can be therapeutically targeted with specific inhibitors such as plerixafor or GMI-1271 (uproleselan). However, in the absence of approved targeted therapies supportive treatment with the uric acid lowering agents allopurinol and rasburicase as well as aggressive intravenous fluid hydration for the treatment and prophylaxis of TLS, transfusion of blood products for the management of DIC, and cytoreduction with intensive chemotherapy, leukapheresis, or hydroxyurea remain the mainstay of therapy for AML patients with hyperleukocytosis.

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Section: The Bone Marrow Niche Under Physiologic Conditions and Itmentioning

confidence: 99%

Section: The Bone Marrow Niche Under Physiologic Conditions and Itmentioning

confidence: 99%

Hyperleukocytosis and Leukostasis in Acute Myeloid Leukemia: Can a Better Understanding of the Underlying Molecular Pathophysiology Lead to Novel Treatments?

Bewersdorf

Zeidan

2020

Cells

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“…1). Even though the primary role of adhesion molecules is to maintain cell-to-cell contact and attachment to the extracellular matrix, they also function as signaling effector molecules involved in cellular functions, such as cell growth, survival, and transcriptional activity (5)(6)(7). In this review, we will focus on describing the distinct roles that the two major groups of adhesion molecules, cadherins and integrins, play in cancer biology.…”

mentioning

confidence: 99%

Cell adhesion in cancer: Beyond the migration of single cells

Janiszewska

Primi

Izard

2020

Journal of Biological Chemistry

392

275

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Homeostasis in healthy tissues strongly relies on cell-to-cell adhesion and cell-to-extracellular matrix interactions. For instance, normal epithelial cells maintain tissue structure by adhering to each other and to the extracellular matrix. The proteins that mediate these distinct interactions are collectively called cell adhesion molecules and are divided into four major groups: cadherins, integrins, selectins, and immunoglobulins. They not only physically anchor cells, but also critically integrate signaling between the extracellular microenvironment and cells. These signals include biochemical cues, as adhesion proteins can both act as ligand-activated receptors and activate mechanotransduction triggered by changes in the physical environment. Molecular mechanisms related to cell adhesion signaling have been extensively studied, especially because mutations and changes in expression of these proteins, particularly cadherins and integrins, are frequently associated with diseases ranging from developmental intellectual disability to cancer. In fact, two major hallmarks of cancer, loss of cell-to-cell adhesion and anchorage-independent growth, are both dependent on cell adhesion molecules. Despite many studies elucidating the relationships between malignant transformation and metastasis and cellular adhesion processes, several areas still await exploration. Here, we highlight recently discovered roles of adhesion molecules in collective cancer cell migration and discuss the utility of three-dimensional models in studying cell-cell adhesion. We also describe recent therapeutic approaches targeting adhesion molecules.

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“…Leukocyte transendothelial migration. As fa as we know, CAMs take part in the process of integrating differentiation, proliferation and pro-survival signals from the surrounding microenvironment to the inner cell, which enables the numerous cell-cell and cell-matrix interactions within the bone marrow microenvironment and the controlled lifelong self-renewal and progeny of hematopoietic stem and progenitor cells [27]. Leukocyte transendothelial migration is generally activated in cancer progression, which hampers the anti-tumor responses of the host [28].…”

Section: Discussionmentioning

confidence: 99%

Candidate biomarkers and gene modules investigation for bone tumor samples derived from castration-resistant prostate cancer bone metastasis patients using WGCNA

Yu¹,

Zou²,

Wang³

et al. 2019

Preprint

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Background About 80-90% of castration-resistant prostate cancer (CRPC) patients would develop bone metastasis, which leads to the disorder of bone metabolism and induces skeletal related events. However, except for the few approved radiotherapeutic and chemotherapy drugs, like radium-223 and denosumab, there is still lack of effective treatment targeting the bone metastatic tumor. It is necessary and significant to explore the mechanisms of bone metastasis and tumorigenesis, especially the differences between the tumor and normal cells in bone after metastatic colonization, which will provide a set of candidate genes for the screening of novel bone targeting agents.Results 4 datasets (GSE32269, GSE101607, GSE29650 and GSE74685) were obtained from the GEO database. 1983 differentially expressed genes (DEGs) were first identified between bone marrow tumor samples and normal marrow samples in GSE32269, followed by the weighted gene co-expression analysis. Most of the top 10 DEGs are found to be related with prostate cancer. 7 co-expression modules were then detected based on the 1469 DEGs shared by the 4 datasets, and 3 of them were found highly preserved among the other three datasets. The top 30 hub genes of the 3 modules were extracted. Among the enriched pathways of preserved modules, Cell adhesion molecules (CAMs) and Leukocyte transendothelial migration might play significant important roles in the tumor development in bone marrow. Literature searches further showed that a set of DEGs and hub genes might also contribute to the development of tumor in bone.Conclusions Together, our findings not only provide outline of expression profile in CRPC bone metastasis, but also screen a set of genes associated with CPRC tumor cell colonization and development of bone tumor, which could be helpful for novel bone targeting agents screening.

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Oncogenic Deregulation of Cell Adhesion Molecules in Leukemia

Cited by 32 publications

References 124 publications

Hyperleukocytosis and Leukostasis in Acute Myeloid Leukemia: Can a Better Understanding of the Underlying Molecular Pathophysiology Lead to Novel Treatments?

Hyperleukocytosis and Leukostasis in Acute Myeloid Leukemia: Can a Better Understanding of the Underlying Molecular Pathophysiology Lead to Novel Treatments?

Cell adhesion in cancer: Beyond the migration of single cells

Candidate biomarkers and gene modules investigation for bone tumor samples derived from castration-resistant prostate cancer bone metastasis patients using WGCNA

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