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EMD originates from hyaluronan-induced homophilic interactions of CD44 variant-expressing MM cells under shear stress.

Extramedullary disease (EMD) is known to be associated with chemoresistance and poor prognosis in multiple myeloma (MM); however, the mechanisms of its development are not fully understood. Elucidating the mechanism of EMD development and its therapeutic targeting would greatly contribute to further improvement of treatment outcome in patients with MM. Here, we show that bone marrow stroma cell-derived hyaluronan (HA) elicits homophilic interactions of MM cells by binding to surface CD44, especially long-stretch variants, under physiological shear stress and generates cell clusters that might

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… MM cells express various adhesion molecules, such as CD29 (β1-integrin), CD44, CD49d (β4-integrin, a subunit of VLA-4), CD49e (β5-integrin, a subunit of VLA-5), CD54 (ICAM-1), CD56 (NCAM), CD138 (syndecan-1), CD184 (CXCR4), and CD319 (SLAMF7), which play redundant roles in interacting with the BM microenvironment …

Cancer metastasis to the bone: Mechanisms and animal models (Review).

The majority of cancer-related deaths result from tumor metastasis, with bone metastasis occurring in almost all types of malignant tumors. Understanding the mechanism by which tumors metastasize to bone is critical for the identification of novel therapeutic targets. A large amount of research has been carried out using animal models, and these models have been crucial in advancing the fundamental understanding of cancer. However, current models are limited; although they can mimic specific stages of the metastatic process, they are not able to replicate the entire process from tumorigenesis

Emerging Roles of Osteoclasts in the Modulation of Bone Microenvironment and Immune Suppression in Multiple Myeloma.

Multiple myeloma (MM) is one of the most common forms of hematologic malignancy resulting from cancerous proliferation of mature malignant plasma cells (MPCs). But despite the real improvement in therapeutics in the past years, it remains largely incurable. MM is the most frequent cancer to involve bone due to the stimulation of osteoclast (OCL) differentiation and activity. OCLs have a unique capacity to resorb bone. However, recent studies reveal that they are not restrained to this sole function. They participate in the control of angiogenesis, medullary niches, and immune responses, includ

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… CD138 (syndecan-1) is a proteoglycan that binds growth factors, chemokines, cytokines, and extracellular matrix components and regulates the interactions between MPCs and their environment ( 22 , 23 ). …

Multiple myeloma cancer stem cells.

Multiple myeloma (MM) remains incurable despite much progress that has been made in the treatment of the disease. MM cancer stem cell (MMSC), a rare subpopulation of MM cells with the capacity for self-renewal and drug resistance, is considered to lead to disease relapse. Several markers such as side population (SP) and ALDH1+ have been used to identify MMSCs. However, ideally and more precisely, the identification of the MMSCs should rely on MMSCs phenotype. Unfortunately the MMSC phenotype has not been properly defined yet. Drug resistance is the most important property of MMSCs and contribu

CAR T-Cells in Multiple Myeloma: State of the Art and Future Directions.

Despite recent therapeutic advances, the prognosis of multiple myeloma (MM) patients remains poor. Thus, new strategies to improve outcomes are imperative. Chimeric antigen receptor (CAR) T-cell therapy has changed the treatment landscape of B-cell malignancies, providing a potentially curative option for patients who are refractory to standard treatment. Long-term remissions achieved in patients with acute lymphoblastic leukemia and Non-Hodgkin Lymphoma encouraged its further development in MM. B-cell maturation antigen (BCMA)-targeted CAR T-cells have established outstanding results in heavi

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… APRIL, and TACI Interact with syndecan-1 on the surface of multiple myeloma cells to form an essential survival loop. Eur J Haematol. (2009) 83:119–29. 10.1111/j.1600-0609.2009.01262.x 32. Neri P, Kumar S, Fulciniti MT, Vallet S, Chhetri S, Mukherjee S, et al. … Chemotherapy stimulates syndecan-1 shedding: a potentially negative effect of treatment that may promote tumor relapse. Matrix Biol J Int Soc Matrix Biol. (2014) 35:215–22. 10.1016/j.matbio.2013.10.005 104. Barber A, Meehan KR, Sentman CL. …

Chemotherapy-Induced Tissue Injury: An Insight into the Role of Extracellular Vesicles-Mediated Oxidative Stress Responses.

The short- and long-term side effects of chemotherapy limit the maximum therapeutic dose and impair quality of life of survivors. Injury to normal tissues, especially chemotherapy-induced cardiomyopathy, is an unintended outcome that presents devastating health impacts. Approximately half of the drugs approved by the Food and Drug Administration for cancer treatment are associated with the generation of reactive oxygen species, and Doxorubicin (Dox) is one of them. Dox undergoes redox cycling by involving its quinone structure in the production of superoxide free radicals, which are thought to

CAR-T cell therapy for treatment-refractory rheumatic autoimmune diseases: a systematic review of clinical outcomes and safety profiles.

OBJECTIVES: Current therapeutic paradigms for treatment-refractory rheumatic diseases rely on chronic immunosuppression with variable efficacy and potential for cumulative toxicity. We systematically synthesised evidence on the clinical efficacy, safety and durability of chimeric antigen receptor T-cell (CAR-T) therapy in autoimmune rheumatic diseases. METHODS: We conducted a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO: CRD42025641602). Five databases were searched from inception to February 2025 for primary studies inves

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… BCR, B-cell receptor; CD138, Syndecan-1; CRP, C-reactive protein; DAS28, Disease Activity Score 28; HLA-II, Human leukocyte antigen class II; HAQ, Health Assessment Questionnaire; IL, interleukin; PI3K/AKT, intracellular signalling molecules; TNF-α, tumour necrosis factor-alpha; ZAP-70, Zeta-chain-associated …

TGF-β: an active participant in the immune and metabolic microenvironment of multiple myeloma : TGF-β in the microenvironment of multiple myeloma.

Although substantial quantities of potent therapies for multiple myeloma (MM) have been established, MM remains an incurable disease. In recent years, our understanding of the initiation, development, and metastasis of cancers has made a qualitative leap. Cancers attain the abilities to maintain proliferation signals, escape growth inhibitors, resist cell death, induce angiogenesis, and more importantly, escape anti-tumor immunity and reprogram metabolism, which are the hallmarks of cancers. Besides, different cancers have different tumor microenvironments (TME), thus, we pay more attention to

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… Furthermore, increased soluble syndecan-1 (CD138) levels, which are associated with myeloma cells, have been linked to poor prognoses [ 48 ]. …

BCMA-targeted immunotherapy for multiple myeloma.

B cell maturation antigen (BCMA) is a novel treatment target for multiple myeloma (MM) due to its highly selective expression in malignant plasma cells (PCs). Multiple BCMA-targeted therapeutics, including antibody-drug conjugates (ADC), chimeric antigen receptor (CAR)-T cells, and bispecific T cell engagers (BiTE), have achieved remarkable clinical response in patients with relapsed and refractory MM. Belantamab mafodotin-blmf (GSK2857916), a BCMA-targeted ADC, has just been approved for highly refractory MM. In this article, we summarized the molecular and physiological properties of BCMA as

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… For example, APRIL interacts with CD138/syndecan-1 and heparan sulfate proteoglycans (HSPG) to promote proliferation and survival of MM cells [ 56 ]. Concomitant blockade of FGF-R3 and JAK2 leads to BCMA downregulation [ 57 ]. … APRIL and TACI interact with syndecan-1 on the surface of multiple myeloma cells to form an essential survival loop. Eur J Haematol. 2009;83(2):119–129. doi: 10.1111/j.1600-0609.2009.01262.x. 47. Bolkun L, Lemancewicz D, Jablonska E, Kulczynska A, Bolkun-Skornicka U, Kloczko J, Dzieciol J. …

Prevention Of Skeletal Related Events In Multiple Myeloma: Focus On The RANK-L Pathway In The Treatment Of Multiple Myeloma.

More than 90% of patients with multiple myeloma (MM) have osteolytic bone lesions which increase the risk of skeletal-related events (SRE). The cytokine milieu in the bone marrow microenvironment (BMME) of MM plays a key role in myeloma bone disease by impairing the balance between osteoclastogenesis and osteoblastogenesis. This is orchestrated by the malignant plasma cell (MPC) with the ultimate outcome of MPC proliferation and survival at the expense of excess osteoclast activation resulting in osteolytic bone lesions. Prevention of SRE is currently accomplished by the inhibition of osteocla

Identification of Key Genes and Pathways in Myeloma side population cells by Bioinformatics Analysis.

Background: Multiple myeloma (MM) is the second most common hematological malignancy, which is still incurable and relapses inevitably, highlighting further understanding of the possible mechanisms. Side population (SP) cells are a group of enriched progenitor cells showing stem-like phenotypes with a distinct low-staining pattern with Hoechst 33342. Compared to main population (MP) cells, the underlying molecular characteristics of SP cells remain largely unclear. This bioinformatics analysis aimed to identify key genes and pathways in myeloma SP cells to provide novel biomarkers, predict MM

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… Syndecan-1 expression suppresses the level of myeloma matrix metalloproteinase-9. Br J Haematol. 1999;104:365–73. doi: 10.1046/j.1365-2141.1999.01180.x. 81. Vacca A, Ribatti D, Presta M, Minischetti M, Iurlaro M, Ria R. et al. …

Drug Conjugated and Bispecific Antibodies for Multiple Myeloma: Improving Immunotherapies off the Shelf.

The impressive improvement of overall survival in multiple myeloma (MM) patients in the last years has been mostly related to the availability of new classes of drugs with different mechanisms of action, including proteasome inhibitors (PI), immunomodulating agents (IMiDs), and monoclonal antibodies. However, even with this increased potence of fire, MM still remains an incurable condition, due to clonal selection and evolution of neoplastic clone. This concept underlines the importance of immunotherapy as one of the most relevant tools to try to eradicate the disease. In line with this concep

Therapeutic potential of Fingolimod in triple negative breast cancer preclinical models.

Surgery followed by a chemotherapy agent is the first-line treatment for breast cancer patients. Nevertheless, new targets are required for women with triple-negative breast cancer (TNBC) in order to improve the treatment of this aggressive cancer subtype. Multiple pro-inflammatory molecules including lipid-based substances such as sphingosine-1-phosphate (S1P) promote cancer progression. In this preclinical study, we aim to investigate the efficacy of Fingolimod, an inhibitor of S1P / S1P receptors axis, already approved as an immunomodulator in multiple sclerosis. The impact of Fingolimod wa

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… Sphingosine-1-phosphate induced epithelial-mesenchymal transition of hepatocellular carcinoma via an MMP-7/syndecan-1/TGF-β autocrine loop. Oncotarget. 2016;7:63324–63337. doi: 10.18632/oncotarget.11450. 8. Hirose Y., Nagahashi M., Katsuta E., Yuza K., Miura K., Sakata J. …

Monoclonal antibodies in the treatment of multiple myeloma: current status and future perspectives.

The treatment landscape for patients with multiple myeloma (MM) is constantly evolving. Over the past decade, the introduction of novel agents such as proteasome inhibitors and immunomodulatory drugs has led to notable changes in therapeutic strategy, and improvements in survival, yet MM remains incurable in the vast majority of cases. More recently, a targeted approach to MM treatment has emerged, using monoclonal antibodies (mAbs) to target antigens expressed on the surface of MM cells. MAbs tested to date kill MM cells via the host's immune system and/or by promoting apoptosis, and appear t

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… CD138 CD138/syndecan-1 is expressed during B-cell development, and is specifically located on plasma cells and MM cells in the bone marrow. 87 Indatuximab ravtansine (BT062) comprises a mAb against CD138 conjugated to the cytotoxic maytansinoid DM4. 88 As a monotherapy, indatuximab ravtansine treatment …

Нанозимы: инновационная терапия в борьбе с нейродегенеративными заболеваниями.

Нейродегенеративные заболевания, включая болезнь Альцгеймера (AD), болезнь Паркинсона (PD), множественный склероз (MS), амиотропический боковой склероз (ALS) и болезнь Хантингтона (HD), представляют собой серьезную проблему для здоровья населения мира из-за их прогрессивного характера и отсутствия лечения. Эти расстройства характеризуются окислительным стрессом, завязыванием белка и нейроинфламмацией, которые в совокупности приводят к нервным повреждениям и смерти. Последние достижения в нанотехнологии позволили внедрить нанозменные наноматериалы, которые имитируют деятельность, похожую на фер

Novel Developments in the Treatment of Multiple Myeloma-Associated Bone Disease.

Osteolytic bone disease is present in about 80% of patients with multiple myeloma at the time of diagnosis. Managing bone disease in patients with multiple myeloma is a challenge and requires a multi-faceted treatment approach with medication, surgery, and radiation. The established treatments with intravenous or subcutaneous antiresorptives can cause debilitating adverse events for patients, mainly osteonecrosis of the jaw, which, traditionally, has been difficult to manage. Now, oral surgery is recommended and proven successful in 60-85% of patients. Patients with spinal involvement may bene

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… MM cells additionally express syndecan-1, which binds OPG, resulting in its endocytosis and degradation, further contributing to osteoclastogenesis [ 97 ]. …

Carbohydrate Targets for CAR T Cells in Solid Childhood Cancers.

Application of the CAR targeting strategy in solid tumors is challenged by the need for adequate target antigens. As a consequence of their tissue origin, embryonal cancers can aberrantly express membrane-anchored gangliosides. These are carbohydrate molecules consisting of a glycosphingolipid linked to sialic acids residues. The best-known example is the abundant expression of ganglioside GD2 on the cell surface of neuroblastomas which derive from GD2-positive neuroectoderm. Gangliosides are involved in various cellular functions, including signal transduction, cell proliferation, differentia

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… Chondroitin sulfate chains normally restricted to the placenta are found on many cancer-associated proteoglycans, including CSPG4, syndecan-1,−4, CD44, and glypican-1, with widespread expression also in pediatric tumors ( 120 ). …

Current trends in theranostic applications of extracellular vesicles in cancer.

BackgroundExtracellular vesicles (EVs) play an integral role in cancer biology, influencing tumor progression, metastasis, and tumor microenvironment. Due to their distinctive molecular composition, including proteins, nucleic acids, and lipids, EVs present a promising candidate for cancer diagnostics and precision therapeutics.MethodsThis review was conducted by looking up recent studies obtained through PubMed, Scopus, and Web of Science databases using targeted keywords such as "Extracellular Vesicles," "Cancer Therapy," "Biomarkers," "Exosomes," "Tumor Microenvironment," and "Precision Med

Mesenchymal stem cells lineage and their role in disease development.

BackgroundMesenchymal stem cells (MSCs) are widely dispersed in vivo and are isolated from several tissues, including bone marrow, heart, body fluids, skin, and perinatal tissues. Bone marrow MSCs have a multidirectional differentiation potential, which can be induced to differentiate the medium in a specific direction or by adding specific regulatory factors. MSCs repair damaged tissues through lineage differentiation, and the ex vivo transplantation of bone marrow MSCs can heal injured sites. MSCs have different propensities for lineage differentiation and pathological evolution for differen

Notch signaling deregulation in multiple myeloma: A rational molecular target.

Despite recent therapeutic advances, multiple myeloma (MM) is still an incurable neoplasia due to intrinsic or acquired resistance to therapy. Myeloma cell localization in the bone marrow milieu allows direct interactions between tumor cells and non-tumor bone marrow cells which promote neoplastic cell growth, survival, bone disease, acquisition of drug resistance and consequent relapse. Twenty percent of MM patients are at high-risk of treatment failure as defined by tumor markers or presentation as plasma cell leukemia. Cumulative evidences indicate a key role of Notch signaling in multiple