Cell Adhesion Regulates CDC25A Expression and Proliferation in Acute Myeloid Leukemia (original) (raw)
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2000
In order to evaluate putative changes of major adhesion molecule expression on plasma cells (PCs) associated with malignant transforma tion, tumor spreading, and immortalization, we have quantified and com pared the expression of CD56, CD44, CDlla, CD49e, and CD45 RO/RA on normal PCs, malignant PCs from multiple myeloma patients in chronic phase, in accelerated phase with or without extramedullary progression,
Adhesion Deregulation in Acute Myeloid Leukaemia
Cells
Cell adhesion is a process through which cells interact with and attach to neighboring cells or matrix using specialized surface cell adhesion molecules (AMs). Adhesion plays an important role in normal haematopoiesis and in acute myeloid leukaemia (AML). AML blasts express many of the AMs identified on normal haematopoietic precursors. Differential expression of AMs between normal haematopoietic cells and leukaemic blasts has been documented to a variable extent, likely reflecting the heterogeneity of the disease. AMs govern a variety of processes within the bone marrow (BM), such as migration, homing, and quiescence. AML blasts home to the BM, as the AM-mediated interaction with the niche protects them from chemotherapeutic agents. On the contrary, they detach from the niches and move from the BM into the peripheral blood to colonize other sites, i.e., the spleen and liver, possibly in a process that is reminiscent of epithelial-to-mesenchymal-transition in metastatic solid cancer...
Bone marrow malignancies as paradigms of dysfunctional cell adhesion mechanisms
Journal of Hematological Malignancies, 2012
In adult bone marrow (BM), hematopoietic stem/progenitor cells (HSPCs) reside in micro-environments which provide instructions for self-renewal, survival, proliferation, differentiation and migration. Adequate response to such complex signals implies communication between HSCs, BM stroma and extracellular matrix molecules (ECM). This is achieved mainly through adhesion molecules. Malignant hematopoietic cells also interact with the BM microenvironment, which provides them with proliferative and survival advantages. Most of the studies on haematological diseases describe cell-ECM interactions as key mechanisms in tumor progression, while genetic alterations of HSC are considered major initiators of the malignant process. However, accumulating evidence suggests that an altered BM microenvironment provides anomalous cell adhesion signals, facilitating tumor initiation. Myeloproliferative and myelodysplastic syndromes are good examples of haematological disorders where alterations in BM microenvironment may play an important role in disease initiation. This review discusses the role for adhesion signals in regulating the BM microenvironment in normalcy and disease.
Adhesion structures in leukemia cells and their regulation by Src family kinases
Cell Adhesion & Migration, 2017
Interaction of leukemia blasts with the bone marrow extracellular matrix often results in protection of leukemia cells from chemotherapy and in persistence of the residual disease which is on the basis of subsequent relapses. The adhesion signaling pathways have been extensively studied in adherent cells as well as in mature haematopoietic cells, but the adhesion structures and signaling in haematopoietic stem and progenitor cells, either normal or malignant, are much less explored. We analyzed the interaction of leukemia cells with fibronectin (FN) using interference reflection microscopy, immunofluorescence, measurement of adherent cell fraction, real-time microimpedance measurement and live cell imaging. We found that leukemia cells form very dynamic adhesion structures similar to early stages of focal adhesions. In contrast to adherent cells, where Src family kinases (SFK) belong to important regulators of focal adhesion dynamics, we observed only minor effects of SFK inhibitor dasatinib on leukemia cell binding to FN. The relatively weak involvement of SFK in adhesion structure regulation might be associated with the lack of cytoskeletal mechanical tension in leukemia cells. On the other hand, active Lyn kinase was found to specifically localize to leukemia cell adhesion structures and a less firm cell attachment to FN was often associated with higher Lyn activity (this unexpectedly occurred also after cell treatment with the inhibitor SKI-1). Lyn thus may be important for signaling from integrin-associated complexes to other processes in leukemia cells.
Tumor Biology
Some surface markers are used to discriminate certain leukemic subpopulations that retain a greater oncogenic potential than others, and, for this reason, they were termed as leukemic stem cells, similar to the concept of cancer stem cells in carcinoma. Among these surface markers are proteins involved in cell–cell adhesion or cell–matrix adhesion, and they may play a role in the relapse of leukemia, similar to metastasis in carcinomas. The most important are epithelial cadherin, neural cadherin, epithelial cell-adhesion molecule, and CD44, which can be cleaved and released, and their soluble forms were found increased in serum levels of cancer patients, being implicated, in some cases, with progression, metastases, and relapse. In this review, we highlighted the role of these four adhesion molecules in carcinomas and hematological malignancies, mainly leukemia, and discuss if the serum levels of soluble forms can be correlated with the surface protein status on the leukemic cells. ...
Blood, 1994
The transmembrane glycoprotein CD34 shows a highly restricted expression on a crucial subset of hematopoietic cells. We show here that engagement of particular determinants of CD34 can lead to signal transduction and to enhanced adhesiveness of CD34' hematopoietic cells. Monoclonal antibodies (MoAbs) directed against O-sialoglycoprotease-sensitive epitopes of CD34 (OBENDlO, ICH3.81.3C5, MY1 0) but not MoAbs against O-sialoglycoprotease-resistant epitopes (9F2, 8 6 1 2) induce actin polymerization in KG-la and KG-l cells and strongly enhanced cytoadhesiveness. The capacity to induce adhesion requires cellular energy, divalent cations, and in-T
The role of cell adhesion molecule in cancer progression and its application in cancer therapy
Acta biochimica Polonica, 2004
Multiple and diverse cell adhesion molecules take part in intercellular and cell-extracellular matrix interactions of cancer. Cancer progression is a multi-step process in which some adhesion molecules play a pivotal role in the development of recurrent, invasive, and distant metastasis. A growing body of evidence indicates that alterations in the adhesion properties of neoplastic cells play a pivotal role in the development and progression of cancer. Loss of intercellular adhesion and the desquamation of cells from the underlying lamina propria allows malignant cells to escape from their site of origin, degrade the extracellular matrix, acquire a more motile and invasion phenotype, and finally, invade and metastasize. In addition to participating in tumor invasiveness and metastasis, adhesion molecules regulate or significantly contribute to a variety of functions including signal transduction, cell growth, differentiation, site-specific gene expression, morphogenesis, immunologic ...