Signaling Pathway Mediating Myeloma Cell Growth and Survival

Hideshima, Teru; Anderson, Kenneth C.

doi:10.3390/cancers13020216

Cited by 48 publications

(45 citation statements)

References 127 publications

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“…VLA-4, LFA-1, MUC-1, or CD40 present on MM cells bind to VCAM-1, ICAM-1, or CD40L on MSCs. Adhesion of tumor cells to MSCs activates many pathways resulting in an induction of cell cycle progression and anti-apoptotic proteins, and inhibition of pro-apoptotic signaling pathways in MM cells [ 72 , 73 , 74 ].…”

Section: Biological Roles Of Mscs In MM Pathologymentioning

confidence: 99%

“…After binding with their receptors, these interleukins and growth factors trigger in tumor cells the activation of signaling pathways such as the JAK2/STAT3, PI3K/AKT, RAS and the downstream mitogen-activated protein kinase (MAPKs), which provoke not only tumor growth and survival but also drug resistance, migration, and dissemination of myeloma cells [ 72 , 73 ].…”

Section: Biological Roles Of Mscs In MM Pathologymentioning

confidence: 99%

“…Several pieces of evidence have shown that MM-MSCs play an essential role in SFM-DR. The binding of IL-6 produced by MM-MSCs to its receptor on the plasma membrane triggers the activation of MAPK, JAK2/STAT3, and PI3K/AKT pathways, resulting in PC proliferation, survival, and drug resistance [ 5 , 72 ]. Importantly, IL-6 is one of the mediators of dexamethasone resistance in myeloma cells via protein tyrosine phosphatase, nonreceptor type 11 (PTPN11, also known as SHP2) [ 92 , 93 , 94 ].…”

Section: Biological Roles Of Mscs In MM Pathologymentioning

confidence: 99%

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Bone Marrow Mesenchymal Stromal Cells in Multiple Myeloma: Their Role as Active Contributors to Myeloma Progression

Maiso

Mogollón

Ocio

et al. 2021

Cancers

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Multiple myeloma (MM) is a hematological malignancy of plasma cells that proliferate and accumulate within the bone marrow (BM). Work from many groups has made evident that the complex microenvironment of the BM plays a crucial role in myeloma progression and response to therapeutic agents. Within the cellular components of the BM, we will specifically focus on mesenchymal stromal cells (MSCs), which are known to interact with myeloma cells and the other components of the BM through cell to cell, soluble factors and, as more recently evidenced, through extracellular vesicles. Multiple structural and functional abnormalities have been found when characterizing MSCs derived from myeloma patients (MM-MSCs) and comparing them to those from healthy donors (HD-MSCs). Other studies have identified differences in genomic, mRNA, microRNA, histone modification, and DNA methylation profiles. We discuss these distinctive features shaping MM-MSCs and propose a model for the transition from HD-MSCs to MM-MSCs as a consequence of the interaction with myeloma cells. Finally, we review the contribution of MM-MSCs to several aspects of myeloma pathology, specifically to myeloma growth and survival, drug resistance, dissemination and homing, myeloma bone disease, and the induction of a pro-inflammatory and immunosuppressive microenvironment.

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Section: Biological Roles Of Mscs In MM Pathologymentioning

confidence: 99%

Section: Biological Roles Of Mscs In MM Pathologymentioning

confidence: 99%

Section: Biological Roles Of Mscs In MM Pathologymentioning

confidence: 99%

See 1 more Smart Citation

Bone Marrow Mesenchymal Stromal Cells in Multiple Myeloma: Their Role as Active Contributors to Myeloma Progression

Maiso

Mogollón

Ocio

et al. 2021

Cancers

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“…They modulate adjacent cells to support their growth and drug resistance via production of cytokines, chemokines, and other cofactors. These messengers trigger signaling cascades including NF-κB, JAK2/STAT3, Hedgehog, Notch, TGFβ-, and Wnt pathway [ 11 ]. Furthermore, molecules within the RAS/RAF/MEK/ERK as well as the PI3K/AKT-pathway are evolving as promising therapeutic targets [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Multiple Myeloma Inhibitory Activity of Plant Natural Products

Jöhrer

Ҫiҫek

2021

Cancers

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A literature search on plant natural products with antimyeloma activity until the end of 2020 resulted in 92 compounds with effects on at least one human myeloma cell line. Compounds were divided in different compound classes and both their structure–activity-relationships as well as eventual correlations with the pathways described for Multiple Myeloma were discussed. Each of the major compound classes in this review (alkaloids, phenolics, terpenes) revealed interesting candidates, such as dioncophyllines, a group of naphtylisoquinoline alkaloids, which showed pronounced and selective induction of apoptosis when substituted in position 7 of the isoquinoline moiety. Interestingly, out of the phenolic compound class, two of the most noteworthy constituents belong to the relatively small subclass of xanthones, rendering this group a good starting point for possible further drug development. The class of terpenoids also provides noteworthy constituents, such as the highly oxygenated diterpenoid oridonin, which exhibited antiproliferative effects equal to those of bortezomib on RPMI8226 cells. Moreover, triterpenoids containing a lactone ring and/or quinone-like substructures, e.g., bruceantin, whitaferin A, withanolide F, celastrol, and pristimerin, displayed remarkable activity, with the latter two compounds acting as inhibitors of both NF-κB and proteasome chymotrypsin-like activity.

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“…MM is highly dependent on the bone marrow microenvironment [18,19] . In recent years, research efforts have focused on understanding the role of the MM tumor microenvironment in MM to identify new targets and develop novel therapeutic approaches.…”

Section: Introductionmentioning

confidence: 99%

The multifunctional role of Notch signaling in multiple myeloma

Sabol¹,

Delgado‐Calle²

2021

JCMT

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Multiple myeloma (MM) is a hematologic cancer characterized by uncontrolled growth of malignant plasma cells in the bone marrow and currently is incurable. The bone marrow microenvironment plays a critical role in MM. MM cells reside in specialized niches where they interact with multiple marrow cell types, transforming the bone/bone marrow compartment into an ideal microenvironment for the migration, proliferation, and survival of MM cells. In addition, MM cells interact with bone cells to stimulate bone destruction and promote the development of bone lesions that rarely heal. In this review, we discuss how Notch signals facilitate the communication between adjacent MM cells and between MM cells and bone/bone marrow cells and shape the microenvironment to favor MM progression and bone disease. We also address the potential and therapeutic approaches used to target Notch signaling in MM.

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Signaling Pathway Mediating Myeloma Cell Growth and Survival

Cited by 48 publications

References 127 publications

Bone Marrow Mesenchymal Stromal Cells in Multiple Myeloma: Their Role as Active Contributors to Myeloma Progression

Bone Marrow Mesenchymal Stromal Cells in Multiple Myeloma: Their Role as Active Contributors to Myeloma Progression

Multiple Myeloma Inhibitory Activity of Plant Natural Products

The multifunctional role of Notch signaling in multiple myeloma

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