αvβ3 integrin engagement modulates cell adhesion, proliferation, and protease secretion in human lymphoid tumor cells

Vacca, Angelo; Ria, Roberto; Presta, Marco; Ribatti, Doménico; Iurlaro, Monica; Merchionne, Francesca; Tanghetti, Elena; Dammacco, Franco

doi:10.1016/s0301-472x(01)00674-9

Cited by 74 publications

(54 citation statements)

References 32 publications

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“…This may be of importance because previous studies of avb3 integrin in multiple myeloma have emphasized its role in tumor proliferation and aggressiveness. Interestingly, avb3 integrin has been shown to be involved in myeloma cell adherence to vitronectin and fibronectin (40). It was further shown that plasma cells interacting with vitronectin and fibronectin via the avb3 integrin recruit MAPK/ERK1/2 and enhance proliferation and matrix metalloproteinase (MMP)-2 and MMP-9, and urokinase-type plasminogen activator secretion (41).…”

Section: Discussionmentioning

confidence: 99%

Thyroid Hormone Is a MAPK-Dependent Growth Factor for Human Myeloma Cells Acting via αvβ3 Integrin

Cohen

Ellis

Khoury

et al. 2011

Molecular Cancer Research

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Experimental and clinical observations suggest that thyroid hormone [L-thyroxine (T 4 ) and 3,5,30 -triiodo-Lthyronine (T 3 )] can support cancer cell proliferation. T 3 and T 4 promote both tumor cell division and angiogenesis by activating mitogen-activated protein kinase (MAPK) via binding to a hormone receptor on the avb3 integrin, overexpressed on many cancer cells. We have studied the responsiveness of several MM cell lines to T 3 and T 4 and characterized hormonal effects on cell survival, proliferation, and MAPK activation. Overnight T 3 (1-100 nmol/L) and T 4 (100 nmol/L) incubation enhanced, up to 50% (P < 0.002), MM cell viability (WST-1 assay) and increased cell proliferation by 30% to 60% (P < 0.01). Short exposure (10 minutes) to T 3 and T 4 increased MAPK activity by 2.5-to 3.5-fold (P < 0.03). Pharmacologic MAPK inhibition blocked the proliferative action of T 3 and T 4 . Antibodies to the integrin avb3 dimer and av and b3 monomers (but not b1) inhibited MAPK activation and subsequent cell proliferation in response to thyroid hormone, indicating dependence upon this integrin. Moreover, tetraiodothyroacetic acid (tetrac), a non-agonist T 4 analogue previously shown to selectively block T 3 /T 4 binding to avb3 receptor site, blocked induction of MAPK by the hormones in a dose-dependent manner. This demonstration of the role of thyroid hormones as growth factors for MM cells may offer novel therapeutic approaches. Mol Cancer Res; 9(10); 1385-94. Ó2011 AACR.

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Section: Discussionmentioning

confidence: 99%

Thyroid Hormone Is a MAPK-Dependent Growth Factor for Human Myeloma Cells Acting via αvβ3 Integrin

Cohen

Ellis

Khoury

et al. 2011

Molecular Cancer Research

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“…The precise regulation of cell-cell and cell-matrix adhesion and control over lipid raft -associated signaling complexes play a crucial role in various aspects of normal T-cell biology, including T-cell homing, T-cell activation, and cell-cell contact formation with target cells (63,(81)(82)(83)(84)(85), whereas in malignant lymphocytes deregulation of these processes may result in increased invasiveness and aggressiveness (75)(76)(77)(78)(79)86). As T-ALLs are frequently highly invasive and in T lymphocytes integrin receptors of the h 1 class are responsible for both cell adhesion to the extracellular matrix component fibronectin and for cell-cell interactions through the cell-membrane ligand such as VCAM-1, our observations suggest that ephrin-B1 may play an important role in regulating the invasiveness of T-ALL cells through the negative control over their cell-cell and cell-matrix interactions.…”

Section: Discussionmentioning

confidence: 99%

“…Molecules regulating cell adhesion may play an important role in the invasiveness and aggressiveness of cancer cells (75)(76)(77)(78)(79). Because our experiments showed that ephrin-B1 suppresses attachment of T-ALL cells, we attempted to determine if ephrin-B1 also controls their invasive behavior.…”

Section: Ephrin-b Signaling Supports Invasiveness Of T-all Cellsmentioning

confidence: 99%

In Human Leukemia Cells Ephrin-B–Induced Invasive Activity Is Supported by Lck and Is Associated with Reassembling of Lipid Raft Signaling Complexes

Jiang

Freywald

Webster

et al. 2008

Molecular Cancer Research

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Proteins of the ephrin-B group operate in nonlymphoid cells through the control of their migration and attachment, and are crucial for the development of the vascular, lymphatic, and nervous systems. Ephrin-B activity is deregulated in various nonlymphoid malignancies; however, their precise role in cancer has only started to be addressed. We show here that ephrin-B1, a member of the ephrin-B group, is expressed in pediatric T-cell leukemias, including leukemia cell line Jurkat. Treatment of Jurkat cells with ephrin-Bstimulating EphB3 enhances ephrin-B1 phosphorylation and induces its relocalization into lipid rafts. These events are mediated by the T lineage -specific kinase, Lck, as ephrin-B1 phosphorylation and lipid raft association are blocked in the Lck-deficient clone of Jurkat, JCAM1.6. Ephrin-B1 also induces colocalization of the CrkL and Rac1 cytoskeleton regulators and initiates in leukemic cells a strong repulsive response. The absence of Lck blocks ephrin-B1 -induced signaling and repulsion, confirming the essential role for Lck in ephrin-B1 -mediated responses. This shows a new role for ephrin-B1 in the regulation of leukemic cells through the Lck-dependent Rac1 colocalization with its signaling partner, CrkL, in lipid rafts. In agreement with its repulsive action, ephrin-B1 seems to support metastatic properties of leukemic cells, as suppression of ephrin-B1 signaling inhibits their invasiveness. Because ephrin-B1 -activating EphB proteins are ubiquitously expressed, our findings suggest that ephrin-B1 is likely to play an important role in the regulation of malignant T lymphocytes through the control of lipid-raftassociated signaling, adhesion, and invasive activity, and therefore may represent a novel target for cancer treatment. (Mol Cancer Res 2008;6(2):291 -305)

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“…28 Fresh bone marrow plasma cells from MM patients are able to interact with immobilized vitronectin and fibronectin through avb3 integrin. 33 This interaction allows their prompt adhesion to the substratum and rapidly induces their recruitment of the b3 integrin subunit together with the cytoskeletal components vinculin and paxillin and results in an increase in MMP-2, MMP-9 and uPA secretion. Podar et al 34 have shown that VEGF stimulates migration of an MM cell line and cell attachment to fibronectin via a1 integrin and protein kinase C activation.…”

Section: Invasive Ability Of Plasma Cellsmentioning

confidence: 99%

Bone marrow angiogenesis in multiple myeloma

2005

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Angiogenesis is a constant hallmark of multiple myeloma (MM) progression and has prognostic potential. It is induced by plasma cells via angiogenic factors with the transition from monoclonal gammopathy of undetermined significance (MGUS) to MM, and probably with loss of angiostatic activity on the part of MGUS. The pathophysiology of MM-induced angiogenesis is complex and involves both direct production of angiogenic cytokines by plasma cells and their induction within the microenvironment. The latter are secreted by stromal cells, endothelial cells (EC) and osteoclasts, and promote plasma cell growth, survival and migration, as well as paracrine cytokine secretion and angiogenesis in the bone marrow milieu. Angiogenesis is also supported by inflammatory cells following their recruitment and activation by plasma cells. Finally, circulating EC and endothelial precursor cells (EPC) contribute to the neovascularization, and the presence of EPC suggests that vasculogenesis (new vessel formation from EPC) may also contribute to the full MM vascular tree.

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αvβ3 integrin engagement modulates cell adhesion, proliferation, and protease secretion in human lymphoid tumor cells

Cited by 74 publications

References 32 publications

Thyroid Hormone Is a MAPK-Dependent Growth Factor for Human Myeloma Cells Acting via αvβ3 Integrin

Thyroid Hormone Is a MAPK-Dependent Growth Factor for Human Myeloma Cells Acting via αvβ3 Integrin

In Human Leukemia Cells Ephrin-B–Induced Invasive Activity Is Supported by Lck and Is Associated with Reassembling of Lipid Raft Signaling Complexes

Bone marrow angiogenesis in multiple myeloma

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