Cooperation between heparin-binding EGF-like growth factor and interleukin-6 in promoting the growth of human myeloma cells

Wang, Yue Dan; Vos, John De; Jourdan, Michel; Couderc, Guilhem; Lu, Zhao-Yang; Rossi, Jean‐François; Klein, Bernard

doi:10.1038/sj.onc.1205355

Cited by 56 publications

(40 citation statements)

References 40 publications

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“…In support of this idea, treatment of HepG2 cells with soluble IL-6Ra in the absence of IL-6 led to a complete inhibition of early growth response protein 1, a gene downstream of ERK activation (61). Similarly, cross-talk between gp130 and/or IL-6Ra and the EGF family receptors has been reported in several tumor cell lines (62)(63)(64)(65)(66) and in primary mammary epithelial cells (67). It is also possible that increased ERK activation in the absence of IL-6Ra is due to indirect effects on the expression or activity of other cytokines or on receptors other than gp130.…”

Section: Discussionmentioning

confidence: 63%

Differences in Wound Healing in Mice with Deficiency of IL-6 versus IL-6 Receptor

McFarland-Mancini

Funk

Paluch

et al. 2010

The Journal of Immunology

224

177

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IL-6 modulates immune responses and is essential for timely wound healing. As the functions mediated by IL-6 require binding to its specific receptor, IL-6Rα, it was expected that mice lacking IL-6Rα would have the same phenotype as IL-6–deficient mice. However, although IL-6Rα–deficient mice share many of the inflammatory deficits seen in IL-6–deficient mice, they do not display the delay in wound healing. Surprisingly, mice with a combined deficit of IL-6 and IL-6Rα, or IL-6–deficient mice treated with an IL-6Rα–blocking Ab, showed improved wound healing relative to mice with IL-6 deficiency, indicating that the absence of the receptor contributed to the restoration of timely wound healing, rather than promiscuity of IL-6 with an alternate receptor. Wounds in mice lacking IL-6 showed delays in macrophage infiltration, fibrin clearance, and wound contraction that were not seen in mice lacking IL-6Rα alone and were greatly reduced in mice with a combined deficit of IL-6 and IL-6Rα. MAPK activation-loop phosphorylation was elevated in wounds of IL-6Rα–deficient mice, and treatment of wounds in these mice with the MEK inhibitor U0126 resulted in a delay in wound healing suggesting that aberrant ERK activation may contribute to improved healing. These findings underscore a deeper complexity for IL-6Rα function in inflammation than has been recognized previously.

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Section: Discussionmentioning

confidence: 63%

Differences in Wound Healing in Mice with Deficiency of IL-6 versus IL-6 Receptor

McFarland-Mancini

Funk

Paluch

et al. 2010

The Journal of Immunology

224

177

View full text Add to dashboard Cite

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“…In the current experiments, cells were cultured at a low concentration to limit the biological activity of autocrine loops involving EGF-ligands. Indeed, we have previously shown that autocrine HB-EGF contributes to the IL-6-induced growth of some IL-6-dependent HMCLs cultured at a high cell density (De Vos et al, 2001;Wang et al, 2002;Mahtouk et al, 2004). Compiling our previous data about ErbB expression in HMCLs with those of EGF-ligand expression, we provide here a comprehensive description of autocrine loops in HMCLs.…”

Section: Discussionmentioning

confidence: 65%

Heparan sulphate proteoglycans are essential for the myeloma cell growth activity of EGF-family ligands in multiple myeloma

et al. 2006

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The epidermal growth factor (EGF)/EGF-receptor (ErbB1-4) family is involved in the biology of multiple myeloma (MM). In particular, ErbB-specific inhibitors induce strong apoptosis of myeloma cells (MMC) in vitro.To delineate the contribution of the 10 EGF-family ligands to the pathogenesis of MM, we have assessed their expression and biological activity. Comparing Affymetrix DNA-microarray-expression-profiles of CD138-purified plasma-cells from 65 MM-patients and 7 normal individuals to those of plasmablasts and B-cells, we found 5/10 EGF-family genes to be expressed in MMC. Neuregulin-2 and neuregulin-3 were expressed by MMC only, while neuregulin-1, amphiregulin and transforming growth factor-a were expressed by both MMC and normal plasma-cells. Using real-time polymerase chain reaction, we found HB-EGF, amphiregulin, neuregulin-1 and epiregulin to be expressed by cells from the bone marrow-environment. Only the EGF-members able to bind heparan-sulphate proteoglycans (HSPGs) -neuregulin-1, amphiregulin, HB-EGF -promote the growth of MMC. Those ligands strongly bind MMC through HSPGs. The binding and the MMC growth activity was abrogated by heparitinase, heparin or deletion of the HS-binding domain. The number of HS-binding EGF ligand molecules bound to MMC was higher than 10 5 molecules/cell and paralleled that of syndecan-1. Syndecan-1, the main HSPG present on MM cells, likely concentrates high levels of HS-binding-EGF-ligands at the cell membrane and facilitates ErbB-activation. Altogether, our data further identify EGF-signalling as promising target for MM-therapy.

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“…In addition, to the importance of HER-2/Neu in ALL, there is a growing body of literature surrounding the EGFR and multiple myeloma [20][21][22][23][24]. Mahtouk et al [24] found HER-2/Neu mRNA to be expressed in 9 myeloma cell lines, while ErbB1, ErbB3 and ErbB4 were only expressed in 3, 6 and 4 of these lines, respectively.…”

Section: In the Development Of Therapeutic Antibodiesmentioning

confidence: 99%

Targeting the EGFR Pathway for Cancer Therapy

Johnston¹,

Navaratnam²,

Pitz³

et al. 2006

CMC

173

116

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Abstract:Clinical studies have shown that HER-2/Neu is over-expressed in up to one-third of patients with a variety of cancers, including B-cell acute lymphoblastic leukemia (B-ALL), breast cancer and lung cancer, and that these patients are frequently resistant to conventional chemo-therapies. Additionally, in most patients with multiple myeloma, the malignant cells over-express a number of epidermal growth factor receptors (EGFR)s and their ligands, HB-EGF and amphiregulin, thus this growth-factor family may be an important aspect in the patho-biology of this disease. These and other, related findings have provided the rationale for the targeting of the components of the EGFR signaling pathways for cancer therapy. Below we discuss various aspects of EGFR-targeted therapies mainly in hematologic malignancies, lung cancer and breast cancer. Beside novel therapeutic approaches, we also discuss specific side effects associated with the therapeutic inhibition of components of the EGFR-pathways. Alongside small inhibitors, such as Lapatinib (Tykerb, GW572016), Gefitinib (Iressa, ZD1839), and Erlotinib (Tarceva, OSI-774), a significant part of the review is also dedicated to therapeutic antibodies (e.g.: Trastuzumab / Herceptin, Pertuzumab / Omnitarg / rhuMab-2C4, Cetuximab / Erbitux / IMC-C225, Panitumumab / Abenix / ABX-EGF, and also ZD6474). In addition, we summarize, both current therapy development driven by antibody-based targeting of the EGFR-dependent signaling pathways, and furthermore, we provide a background on the history and the development of therapeutic antibodies.

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Cooperation between heparin-binding EGF-like growth factor and interleukin-6 in promoting the growth of human myeloma cells

Cited by 56 publications

References 40 publications

Differences in Wound Healing in Mice with Deficiency of IL-6 versus IL-6 Receptor

Differences in Wound Healing in Mice with Deficiency of IL-6 versus IL-6 Receptor

Heparan sulphate proteoglycans are essential for the myeloma cell growth activity of EGF-family ligands in multiple myeloma

Targeting the EGFR Pathway for Cancer Therapy

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