MT2-MMP is differentially expressed in multiple myeloma cells and mediates their growth and progression

Fakhari, Shohreh; Jalili, Ali; Nikkhoo, Bahram; Ghaderi, Bayazid; Boshagh, Mohammad Amin; Mirzaie, Sako; Moradzad, Mohammad

doi:10.1016/j.cellsig.2022.110248

Cited by 4 publications

(6 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Compared to other cohorts [19,31,[33][34][35][36][37], our patients were younger (median of 55 years vs. 65 years), presented more commonly with osteolytic lesions (90% vs 35%) and had more frequently higher levels of LDH (35% vs. 12%). In line with other series [33], combined abnormal cytogenetics analyses were detected in 61.3% of our patients and 22.6% had hyperdiploidy.…”

Section: Discussioncontrasting

confidence: 52%

Clinical Relevance of Interferon Regulatory Family-4 (IRF4) Expression in Newly Diagnosed Patients with Multiple Myeloma

Abdelmonem

Nooh²,

Ashry³

2023

Indian J Hematol Blood Transfus

View full text Add to dashboard Cite

Multiple myeloma (MM) is a malignant plasma cell neoplasm with complex biology and heterogenous course. Interferon regulatory factor 4 (IRF4) transcription factor, important key developmental stages of hematopoiesis, represents an excellent potential therapeutic target. The present work aimed to investigate the expression status of IRF4 in the diagnostic bone marrow biopsy (BMB) cores of MM patients. This prospective study included 62 newly diagnosed MM patients. The expression of IRF4 was assessed in the BMB by immunohistochemistry (IHC). The data were correlated to the patients’ clinico-pathological features, response to treatment and survival rates. IRF4 expression was observed in 50% of MM patients (31/62). IRF-4 positive patients were more frequently male patients (P = 0.018), have immunoglobulin heavy chain (IgH) translocations (P = 0.05) and tended to present with a higher platelets count (P = 0.07). Multiple myeloma patients presenting with urine M-protein had worse overall survival (OS) than negative cases (P = 0.012). Normocellular BM aspirate (BMA) was associated with better OS than hypercellular and hypocellular BMA (P = 0.006). Patchy distribution of plasma cells in BMB was associated with better disease-free survival (DFS) while diffuse infiltration had the worst (P = 0.019). Of note, after treatment, MM patients had significantly lower percentage of BMA plasma cells, platelet count, β2 microglobulin and creatinine levels (P = 0.037, < 0.001, 0.022 and 0.026, respectively). Had higher albumin level (P = 0.007), compared to initial investigations. No significant association was found between IRF4 expression and the patients’clinical outcomes. Patterns of plasma cells distribution in BMB, BMA cellularity and urine M-protein are prognostically relevant in MM.

show abstract

Section: Discussioncontrasting

confidence: 52%

Clinical Relevance of Interferon Regulatory Family-4 (IRF4) Expression in Newly Diagnosed Patients with Multiple Myeloma

Abdelmonem

Nooh²,

Ashry³

2023

Indian J Hematol Blood Transfus

View full text Add to dashboard Cite

show abstract

“…Moreover, it was shown that the migration and invasion of cancer cells were decreased following siRNA induction, which inhibited the endogenous expression of MT2-MMP ( 67 ). In comparison to B cell lines and other normal peripheral blood or BM-derived cells, the expression of MT2-MMP is markedly higher in MM cells, according to a recent study ( 70 ). When MT2-MMP was inhibited in U266 cells utilizing siRNA technology, it turned out to be the case that MT2-MMP siRNA considerably reduced its adhesion, invasion, migration, and proliferation capabilities ( 70 ).…”

Section: The Role Of Mmps In MMmentioning

confidence: 86%

“…In comparison to B cell lines and other normal peripheral blood or BM-derived cells, the expression of MT2-MMP is markedly higher in MM cells, according to a recent study ( 70 ). When MT2-MMP was inhibited in U266 cells utilizing siRNA technology, it turned out to be the case that MT2-MMP siRNA considerably reduced its adhesion, invasion, migration, and proliferation capabilities ( 70 ). Taken together, the studies discussed above suggest that MT2-MMP may serve as a viable biomarker for both diagnosing and treating MM.…”

Section: The Role Of Mmps In MMmentioning

confidence: 86%

“…MT-MMPs are a special subtype that can undergo pericellular proteolysis, which is considered an essential phase in the restructuring of paracancerous tissues ( 67 ). Among MT-MMPs, it has been reported that MT-MMP1 and MT-MMP2, also known as MMP14 and MMP-15, are mainly involved in MM progression ( 68 – 70 ). According to some research, MT1-MMP inhibits macrophage invasion by hydrolyzing ECM elements and cell surface chemicals and by triggering signal transduction pathways that affect motility and energy consumption ( 71 ).…”

Section: The Role Of Mmps In MMmentioning

confidence: 99%

See 1 more Smart Citation

Matrix metalloproteinases and tissue inhibitors in multiple myeloma: promote or inhibit?

Li,

Zhang,

Xiang

et al. 2023

Front. Oncol.

View full text Add to dashboard Cite

Matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) play a vital role in the pathogenesis of multiple myeloma (MM), especially for tumor invasion and osteolytic osteopathy. By breaking down extracellular matrix (ECM) components and releasing the proteins composing the ECM and growth factors, as well as their receptors, MMPs affect tissue integrity and promote cancer cell invasion and metastasis. A vital pathophysiological characteristic of MM is the progress of osteolytic lesions, which are brought on by interactions between myeloma cells and the bone marrow microenvironment. MMPs, certainly, are one of the fundamental causes of myeloma bone disease due to their ability to degrade various types of collagens. TIMPs, as important regulators of MMP hydrolysis or activation, also participate in the occurrence and evolution of MM and the formation of bone disease. This review focuses on the role of MMP-1, MMP-2, MMP-7, MMP-9, MMP-13, MMP-14, and MMP-15 and the four types of TIMPs in the invasion of myeloma cells, angiogenesis, osteolytic osteopathy, to offer some novel perspectives on the clinical diagnostics and therapeutics of MM.

show abstract

“…Membrane-type 1 matrix metalloproteinase (MT1-MMP) interacts with the C1q and C3b components of the complement system and inactivates the complement propagation cascade, protecting tumor cells from the complement-mediated cytolysis (42,43). In addition, it has been demonstrated that MT1-MMP and MT2-MMP are highly expressed in MM cells rather than in normal B cells and plasma cells, and contribute to the degradation of the extracellular matrix and the invasion of MM (44,45). Further experimental work is required to de ne functional relationships of MMPs with complement contributing to pomalidomide resistance in multiple myeloma.…”

Section: Discussionmentioning

confidence: 99%

Multi-omics investigation of the resistance mechanisms of Pomalidomide in Multiple Myeloma

Zhuang

Jiang

et al. 2023

Preprint

View full text Add to dashboard Cite

Background Despite significant therapeutic advances over the last decade, Multiple myeloma remains an incurable disease. Pomalidomide is a second-generation Immunomodulatory drug that is commonly used to treat patients with relapsed/refractory multiple myeloma. However, approximately half of the patients exhibit resistance to pomalidomide treatment. While previous studies have identified Cereblon as a primary target of Immunomodulatory drugs’ anti-myeloma activity, it is crucial to explore additional mechanisms that are currently less understood. Methods To comprehensively investigate the mechanisms of drug resistance, we conducted integrated proteomic and metabonomic analyses of 12 plasma samples from multiple myeloma patients who had varying responses to pomalidomide. Differentially expressed proteins and metabolites were screened, and were further analyzed using pathway analysis and functional correlation analysis. Also, we estimated the cellular proportions based on ssGSEA algorithm. To investigate the potential role of glycine in modulating the response of MM cells to pomalidomide, cell viability and apoptosis were analyzed. Results Our findings revealed a consistent decrease in the levels of complement components in the pomalidomide-resistant group. Additionally, there were significant differences in the proportion of T follicular helper cell and B cells in the resistant group. Furthermore, glycine levels were significantly decreased in pomalidomide-resistant patients, and exogenous glycine administration increased the sensitivity of MM cell lines to pomalidomide. Conclusions These results demonstrate distinct molecular changes in the plasma of resistant patients that could be used as potential biomarkers for identifying resistance mechanisms for pomalidomide in multiple myeloma and developing immune-related therapeutic strategies.

show abstract

MT2-MMP is differentially expressed in multiple myeloma cells and mediates their growth and progression

Cited by 4 publications

References 47 publications

Clinical Relevance of Interferon Regulatory Family-4 (IRF4) Expression in Newly Diagnosed Patients with Multiple Myeloma

Clinical Relevance of Interferon Regulatory Family-4 (IRF4) Expression in Newly Diagnosed Patients with Multiple Myeloma

Matrix metalloproteinases and tissue inhibitors in multiple myeloma: promote or inhibit?

Multi-omics investigation of the resistance mechanisms of Pomalidomide in Multiple Myeloma

Contact Info

Product

Resources

About