The role of IGF-1 as a major growth factor for myeloma cell lines and the prognostic relevance of the expression of its receptor

Sprynski, Anne Catherine; Hose, Dirk; Caillot, L.; Rème, Thierry; Shaughnessy, John D.; Barlogie, Bart; Seckinger, Anja; Moreaux, Jérôme; Hundemer, Michael; Jourdan, Michel; Meißner, Tobias; Jauch, Anna; Mahtouk, Karène; Kassambara, Alboukadel; Bertsch, Uta; Rossi, Jean François; Goldschmidt, Hartmut; Klein, Bernard

doi:10.1182/blood-2008-07-170464

Cited by 152 publications

(153 citation statements)

References 50 publications

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“…With 100 ng/ml insulin, the growth stimulation ranged from 2.1-fold (XG-20) to 18-fold (XG-2). As reported, 4 IGF-1 stimulated HMCLs (Pp0.05), unlike the IGF-1R À HMCLs (XG-10 and XG-12). We show here additional data indicating that IGF-1 growth activity was already significant with 100 pg/ml IGF-1, as for insulin, and became higher with increasing IGF-1 concentrations (Figure 2b).…”

Section: Myeloma Growth Factor Activity Of Insulinmentioning

confidence: 70%

“…We have recently shown that IGF-1 also activates AKT and MAPK phosphorylations in myeloma cells, unlike signal transducer and activator of transcription 3 or nuclear factor-kB. 4 In several experiments, the NVP-AEW541 IGF-1R inhibitor was more efficient in inhibiting AKT and MAPK phosphorylations in XG-2 cells 20 min after insulin activation than the anti-INSR mAb. An explanation is that the IGF-1R inhibitor is a direct IGF-1R kinase inhibitor, likely being more efficient in blocking the 20-min AKT and MAPK phosphorylations than the anti-INSR mAb.…”

Section: Insulin Supports Myeloma Cell Survival and Proliferation Andmentioning

confidence: 99%

“…3 In particular, the MGF activity of interleukin-6 (IL-6), HB-EGF (heparin-binding epidermal growth factor) or hepatocyte growth factor is partly dependant on an IGF-1/IGF-1R loop. 4 IGF-1R is only expressed by the MMCs, unlike normal plasma cells, and patients with IGF-1R present MMCs had a significantly shorter survival than patients with IGF-1R absent MMCs. [4][5][6] Insulin and IGF-1 receptors share 60% overall amino acid sequence homology and 84% homology in their tyrosine kinase domains.…”

Section: Introductionmentioning

confidence: 99%

“…4 IGF-1R is only expressed by the MMCs, unlike normal plasma cells, and patients with IGF-1R present MMCs had a significantly shorter survival than patients with IGF-1R absent MMCs. [4][5][6] Insulin and IGF-1 receptors share 60% overall amino acid sequence homology and 84% homology in their tyrosine kinase domains. 7 They are tetrameric glycoproteins composed of two extracellular a-subunits and two transmembrane b-subunits linked by disulfide bonds.…”

Section: Introductionmentioning

confidence: 99%

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Insulin is a potent myeloma cell growth factor through insulin/IGF-1 hybrid receptor activation

et al. 2010

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Section: Myeloma Growth Factor Activity Of Insulinmentioning

confidence: 70%

Section: Insulin Supports Myeloma Cell Survival and Proliferation Andmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Insulin is a potent myeloma cell growth factor through insulin/IGF-1 hybrid receptor activation

et al. 2010

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“…Therefore, Pim-2 overexpressed in MM cells in the MM bone marrow microenvironment appears to be an important therapeutic target. IGF-1 is another critical microenvironment-derived survival factor for MM cells, 14,15 and inhibition of the IGF-1/PI3K/Akt pathway by Akt or mammalian target of rapamycin inhibitors has drawn considerable attention as a new therapeutic modality against MM. 19,20 Because Pim-2 upregulation is largely independent of the PI3K/Akt pathway (Figure 3e), and because inhibition of Pim-2 and PI3K/Akt pathways cooperatively reduce MM cell survival (Figures 4b and e), Pim-2 should be targeted to improve anti-MM efficacy together with PI3K/Akt pathway inhibitors.…”

Section: Resultsmentioning

confidence: 99%

The serine/threonine kinase Pim-2 is a novel anti-apoptotic mediator in myeloma cells

et al. 2011

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Bone marrow stromal cells (BMSCs) and osteoclasts (OCs) confer multiple myeloma (MM) cell survival through elaborating factors. We demonstrate herein that IL-6 and TNF family cytokines, TNFa, BAFF and APRIL, but not IGF-1 cooperatively enhance the expression of the serine/threonine kinase Pim-2 in MM cells. BMSCs and OCs upregulate Pim-2 expression in MM cells largely via the IL-6/STAT3 and NF-jB pathway, respectively. Pim-2 short interfering RNA reduces MM cell viability in cocultures with BMSCs or OCs. Thus, upregulation of Pim-2 appears to be a novel anti-apoptotic mechanism for MM cell survival. Interestingly, the mammalian target of rapamycin inhibitor rapamycin further suppresses the MM cell viability in combination with the Pim-2 silencing. The Pim inhibitor (Z)-5-(4-propoxybenzylidene) thiazolidine-2, 4-dione and the PI3K inhibitor LY294002 cooperatively enhance MM cell death. The Pim inhibitor suppresses 4E-BP1 phosphorylation along with the reduction of Mcl-1 and c-Myc. Pim-2 may therefore become a new target for MM treatment.

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Maintenance of caecal homeostasis by diverse adaptive immune cells in the rhesus macaque

Castro Dopico,

Guryleva,

Mandolesi

et al. 2024

Clin & Trans Imm

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ObjectivesThe caecum bridges the small and large intestine and plays a front‐line role in discriminating gastrointestinal antigens. Although dysregulated in acute and chronic conditions, the tissue is often overlooked immunologically.MethodsTo address this issue, we applied single‐cell transcriptomic‐V(D)J sequencing to FACS‐isolated CD45+ caecal patch/lamina propria leukocytes from a healthy (5‐year‐old) female rhesus macaque ex vivo and coupled these data to VDJ deep sequencing reads from haematopoietic tissues.ResultsWe found caecal NK cells and ILC3s to co‐exist with a spectrum of effector T cells partially derived from SOX4+ recent thymic emigrants. Tolerogenic Vγ8Vδ1‐T cells, plastic CD4+ T helper cells and GZMK+EOMES+ and TMIGD2+ tissue‐resident memory CD8+ T cells were present and differed metabolically. An IL13+GATA3+ Th2 subset expressing eicosanoid pathway enzymes was accompanied by IL1RL1+GATA3+ regulatory T cells and a minor proportion of IgE+ plasma cells (PCs), illustrating tightly regulated type 2 immunity devoid of ILC2s. In terms of B lymphocyte lineages, caecal patch antigen‐presenting memory B cells sat alongside germinal centre cells undergoing somatic hypermutation and differentiation into IGF1+ PCs. Prototypic gene expression signatures decreased across PC clusters, and notably, expanded IgA clonotypes could be traced in VDJ deep sequencing reads from additional compartments, including the bone marrow, supporting that these cells contribute a steady stream of systemic antibodies.ConclusionsThe data advance our understanding of caecal immunological function, revealing processes involved in barrier maintenance and molecular networks relevant to disease.

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The role of IGF-1 as a major growth factor for myeloma cell lines and the prognostic relevance of the expression of its receptor

Cited by 152 publications

References 50 publications

Insulin is a potent myeloma cell growth factor through insulin/IGF-1 hybrid receptor activation

Insulin is a potent myeloma cell growth factor through insulin/IGF-1 hybrid receptor activation

The serine/threonine kinase Pim-2 is a novel anti-apoptotic mediator in myeloma cells

Maintenance of caecal homeostasis by diverse adaptive immune cells in the rhesus macaque

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