Upregulated expression and function of the α 4 β 1 integrin in multiple myeloma cells resistant to bortezomib

2020 ◽  
Vol 252 (1) ◽  
pp. 29-40 ◽  
Author(s):  
Silvia Sevilla‐Movilla ◽  
Nohemí Arellano‐Sánchez ◽  
Mónica Martínez‐Moreno ◽  
Consuelo Gajate ◽  
Anna Sánchez‐Vencells ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Myeloma Cells ◽  
And Function

scholarly journals Ku86 Variant Expression and Function in Multiple Myeloma Cells Is Associated with Increased Sensitivity to DNA Damage

2000 ◽  
Vol 165 (11) ◽  
pp. 6347-6355 ◽  
Author(s):  
Yu-Tzu Tai ◽  
Gerrard Teoh ◽  
Boris Lin ◽  
Faith E. Davies ◽  
Dharminder Chauhan ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Dna Damage ◽  
Myeloma Cells ◽  
Increased Sensitivity ◽  
And Function

scholarly journals MLN3897, a novel CCR1 inhibitor, impairs osteoclastogenesis and inhibits the interaction of multiple myeloma cells and osteoclasts

Blood ◽  
2007 ◽  
Vol 110 (10) ◽  
pp. 3744-3752 ◽  
Author(s):  
Sonia Vallet ◽  
Noopur Raje ◽  
Kenji Ishitsuka ◽  
Teru Hideshima ◽  
Klaus Podar ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Akt Signaling ◽  
Precursor Cell ◽  
Myeloma Cells ◽  
Osteolytic Bone Disease ◽  
Significant Impairment ◽  
Specific Antagonist ◽  
And Function

Abstract The interaction between osteoclasts (OCs) and multiple myeloma (MM) cells plays a key role in the pathogenesis of MM-related osteolytic bone disease (OBD). MM cells promote OC formation and, in turn, OCs enhance MM cell proliferation. Chemokines are mediators of MM effects on bone and vice versa; in particular, CCL3 enhances OC formation and promotes MM cell migration and survival. Here, we characterize the effects of MLN3897, a novel specific antagonist of the chemokine receptor CCR1, on both OC formation and OC-MM cell interactions. MLN3897 demonstrates significant impairment of OC formation (by 40%) and function (by 70%), associated with decreased precursor cell multinucleation and down-regulation of c-fos signaling. OCs secrete high levels of CCL3, which triggers MM cell migration; conversely, MLN3897 abrogates its effects by inhibiting Akt signaling. Moreover, MM cell-to-OC adhesion was abrogated by MLN3897, thereby inhibiting MM cell survival and proliferation. Our results therefore show novel biologic sequelae of CCL3 and its inhibition in both osteoclastogenesis and MM cell growth, providing the preclinical rationale for clinical trials of MLN3897 to treat OBD in MM.

Betulinic Acid Enhances the Sensitivity of Multiple Myeloma Cells to Bortezomib by the Inactivation of the AKT/mTOR Pathway

2020 ◽  
Vol 18 (3) ◽  
pp. 241-246
Author(s):  
Yu Dan ◽  
Wan Sheng ◽  
Hu Lili
Keyword(s):  
Multiple Myeloma ◽  
Betulinic Acid ◽  
Myeloma Cell ◽  
Mtor Pathway ◽  
Prolonged Treatment ◽  
Myeloma Cells ◽  
Multiple Myeloma Cell ◽  
Increased Sensitivity ◽  
Colony Number ◽  
Rpmi 8226

This study aimed to investigate the mechanism of betulinic acid on multiple myeloma cell resistance to bortezomib. To this end, the bortezomib-resistant RPMI-8226-R cells were generated by prolonged treatment of RPMI-8226 cells with increasing concentrations of bortezomib. Based on the measurements of cell viability and colony number, RPMI-8226-R cells exhibited enhanced resistance to bortezomib than RPMI-8226 cells. Treatment with betulinic acid resulted in increased sensitivity of RPMI-8226-R to bortezomib. When RPMI-8226-R cells were co-treated with bortezomib and betulinic acid, there was an increase in apoptosis rate, cleaved caspase-3, cleaved caspase-9 expression and the decrease in p-AKT/AKT and p-mTOR/mTOR levels. These results suggest that betulinic acid enhances the sensitivity of RPMI-8226-R cells to bortezomib by inhibiting the activation of the AKT/mTOR pathway in bortezomib-resistant multiple myeloma cells.

CD38 as an immunomodulator in cancer

2020 ◽  
Vol 16 (34) ◽  
pp. 2853-2861
Author(s):  
Yanli Li ◽  
Rui Yang ◽  
Limo Chen ◽  
Sufang Wu
Keyword(s):  
Multiple Myeloma ◽  
Cell Activation ◽  
Human Tissues ◽  
Transmembrane Glycoprotein ◽  
Cell Activation Marker ◽  
Research Findings ◽  
A Cell ◽  
And Function ◽  
Human Molecule

CD38 is a transmembrane glycoprotein that is widely expressed in a variety of human tissues and cells, especially those in the immune system. CD38 protein was previously considered as a cell activation marker, and today monoclonal antibodies targeting CD38 have witnessed great achievements in multiple myeloma and promoted researchers to conduct research on other tumors. In this review, we provide a wide-ranging review of the biology and function of the human molecule outside the field of myeloma. We focus mainly on current research findings to summarize and update the findings gathered from diverse areas of study. Based on these findings, we attempt to extend the role of CD38 in the context of therapy of solid tumors and expand the role of the molecule from a simple marker to an immunomodulator.

FTY720 Induces Apoptosis in Multiple Myeloma Cells and Overcomes Drug Resistance

2005 ◽  
Vol 65 (16) ◽  
pp. 7478-7484 ◽  
Author(s):  
Hiroshi Yasui ◽  
Teru Hideshima ◽  
Noopur Raje ◽  
Aldo M. Roccaro ◽  
Norihiko Shiraishi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Drug Resistance ◽  
Myeloma Cells

scholarly journals Hypoxia-induced CREB cooperates MMSET to modify chromatin and promote DKK1 expression in multiple myeloma

Oncogene ◽  
2021 ◽  
Author(s):  
Yinyin Xu ◽  
Jing Guo ◽  
Jing Liu ◽  
Ying Xie ◽  
Xin Li ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Combined Treatment ◽  
Hypoxia Inducible Factor ◽  
Bone Destruction ◽  
Bone Lesions ◽  
Myeloma Cells ◽  
Downstream Target ◽  
Dkk1 Expression

AbstractMyeloma cells produce excessive levels of dickkopf-1 (DKK1), which mediates the inhibition of Wnt signaling in osteoblasts, leading to multiple myeloma (MM) bone disease. Nevertheless, the precise mechanisms underlying DKK1 overexpression in myeloma remain incompletely understood. Herein, we provide evidence that hypoxia promotes DKK1 expression in myeloma cells. Under hypoxic conditions, p38 kinase phosphorylated cAMP-responsive element-binding protein (CREB) and drove its nuclear import to activate DKK1 transcription. In addition, high levels of DKK1 were associated with the presence of focal bone lesions in patients with t(4;14) MM, overexpressing the histone methyltransferase MMSET, which was identified as a downstream target gene of hypoxia-inducible factor (HIF)-1α. Furthermore, we found that CREB could recruit MMSET, leading to the stabilization of HIF-1α protein and the increased dimethylation of histone H3 at lysine 36 on the DKK1 promoter. Knockdown of CREB in myeloma cells alleviated the suppression of osteoblastogenesis by myeloma-secreted DKK1 in vitro. Combined treatment with a CREB inhibitor and the hypoxia-activated prodrug TH-302 (evofosfamide) significantly reduced MM-induced bone destruction in vivo. Taken together, our findings reveal that hypoxia and a cytogenetic abnormality regulate DKK1 expression in myeloma cells, and provide an additional rationale for the development of therapeutic strategies that interrupt DKK1 to cure MM.

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