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Multiple Myeloma Cell-Derived Exosomes: Implications on Tumorigenesis, Diagnosis, Prognosis and Therapeutic Strategies.

Multiple myeloma (MM) is a hematological disease that is still not curable. The bone marrow milieu, with cellular and non-cellular elements, participate in the creation of a pro-tumoral environment enhancing growth and survival of MM plasma cells. Exosomes are vesicles oscillating in dimension between 50 nm and 100 nm in size that can be released by various cells and contribute to the pathogenesis and progression of MM. Exosomes enclose proteins, cytokines, lipids, microRNAs, long noncoding RNAs, and circular RNAs able to regulate interactions between MM plasma cells and adjacent cells. Throug

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… The element of the secretome that is acquiring increasing interest are the extracellular vesicles (EVs) and the exosomes. Exosomes are vesicles originated from cells oscillating in dimension between 50 nm and 100 nm in length with a denseness between 1.13 g/mL and 1.19 g/mL [ 1 ]. …

Human-Induced Pluripotent Stem Cell Models for Amyloid Cardiomyopathy: From Mechanistic Insights to Therapeutic Discovery.

Amyloid cardiomyopathy (ACM), driven by transthyretin (TTR) and immunoglobulin light chain (LC) amyloid fibrils, remains a major clinical challenge due to limited mechanistic understanding and insufficient preclinical models. Human-induced pluripotent stem cells (iPSCs) have emerged as a transformative platform to model ACM, offering patient-specific and genetically controlled systems. In this review, we summarize recent advances in the use of iPSC-derived cardiomyocytes (iPSC-CMs) in both two-dimensional (2D) monolayer cultures and three-dimensional (3D) constructs-including spheroids, organo

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… Additionally, quantitative proteomic analysis of the secretome from these iPSC-HLCs has revealed distinct expression patterns associated with specific TTR variants, providing a scalable and genotype-specific readout for assessing the molecular basis of amyloidogenicity [ 69 ]. …

Cell-based therapy in prophylaxis and treatment of chronic graft-versus-host disease.

Hematopoietic allogeneic stem cell transplantation (allo-SCT) is a curative option for patients with hematological malignancies. However, due to disparities in major and minor histocompatibility antigens between donor and recipient, severe inflammatory complications can occur, among which chronic graft-versus-host disease (cGVHD) can be life-threatening. A classical therapeutic approach to the prevention and treatment of cGVHD has been broad immunosuppression, but more recently adjuvant immunotherapies have been tested. This review summarizes and discusses immunomodulatory approaches with T ce

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… Many hypotheses now center around the belief that it is not the MSCs themselves, but rather their secretome, including extracellular vesicles (EVs) that are driving their therapeutic efficacy. Thus, known as the ‘paracrine hypothesis’. …

P2X7 Рецептор рентгеновских заболеваний: общие молекулярные механизмы и терапевтические последствия.

Редкие заболевания (РЛ) в индивидуальном порядке редко встречаются, но в совокупности они затрагивают большое число людей во всем мире, и подавляющее большинство из них по-прежнему не имеют эффективных методов лечения, позволяющих вести борьбу с заболеваниями. Благодаря достижениям в области геномики и платформ для обмена данными исследования все чаще переходят от одного заболевания к поиску конвергентных молекулярных путей, которые можно было бы использовать в различных клинически отличных друг от друга структурах. В этом контексте purinergic P2X7 рецептор (P2X7R) превратился в предполагаемую

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… Changes induced by P2X7 receptor stimulation of human glioblastoma stem cells in the proteome of extracellular vesicles isolated from their secretome . Cells . 2024 ; 13 ( 7 ): 571 . doi: 10.3390/cells13070571 38607010 PMC11011151 78. Golia MT , Gabrielli M , Verderio C . …

From Cells to Environment: Exploring the Interplay between Factors Shaping Bone Health and Disease.

The skeletal system is an extraordinary structure that serves multiple purposes within the body, including providing support, facilitating movement, and safeguarding vital organs. Moreover, it acts as a reservoir for essential minerals crucial for overall bodily function. The intricate interplay of bone cells plays a critical role in maintaining bone homeostasis, ensuring a delicate balance. However, various factors, both intrinsic and extrinsic, can disrupt this vital physiological process. These factors encompass genetics, aging, dietary and lifestyle choices, the gut microbiome, environment

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… Additionally, MSC secretome, which is collected as conditioned media (CM), is sufficient to exert the therapeutic effects of MSCs [ 144 ]. There is potential for CM to be used as an alternative to the direct implantation of stem cells for bone repairs. …

Sarcopenia in Older Adults with Hematologic Malignancies: A Comprehensive Review of Epidemiology, Prognosis, and Interventions.

Hematologic malignancies, including leukemias, lymphomas, and multiple myeloma, are diseases of older adults (age ≥ 60 years). Treatment decisions in older adults with cancer are heavily influenced by patient fitness: the ability of an individual patient to tolerate the off-target effects of anti-cancer therapy. Sarcopenia, defined as low muscle mass and strength, is increasingly recognized as an important marker of fitness. Furthermore, sarcopenia is known to be modifiable with nutrition and exercise interventions in older adults without cancer, but such evidence is limited for patients with

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… Skeletal muscle is a key metabolic organ for insulin-mediated glucose update, and its secretome (i.e., myokines) has been demonstrated to impact numerous organ systems [ 123 , 124 ]. …

Novel insight and perspectives of nanoparticle-mediated gene delivery and immune-modulating therapies for pancreatic cancer.

Current standard-of-care therapies have failed to improve the survival of patients with metastatic pancreatic cancer (PCA). Therefore, exploring novel therapeutic approaches for cancer targeting is of utmost need. During the past few years, many efforts have been made to develop conventional treatment strategies to reduce chemotherapy resistance. However, critical challenges have impeded current cancer management outcomes, and limited clinical responses have been achieved due to unfavorable off-target effects. Advances in nanotechnology-based gene and immune-modulator delivery systems have exc

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… Cancer-associated fibroblasts (CAFs) Many recent studies have indicated that activated fibroblasts control cancer development by secreting growth factors and ECM as part of their active secretome [ 68 ]. …

Diagnosis and treatment of type 1 diabetes at the dawn of the personalized medicine era.

Type 1 diabetes affects millions of people globally and requires careful management to avoid serious long-term complications, including heart and kidney disease, stroke, and loss of sight. The type 1 diabetes patient cohort is highly heterogeneous, with individuals presenting with disease at different stages and severities, arising from distinct etiologies, and overlaying varied genetic backgrounds. At present, the "one-size-fits-all" treatment for type 1 diabetes is exogenic insulin substitution therapy, but this approach fails to achieve optimal blood glucose control in many individuals. Wit

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… Stem cells as drug delivery methods: application of stem cell secretome for regeneration. Adv Drug Deliv Rev. 2015;82–83:1–11. doi: 10.1016/j.addr.2014.10.007. 151. Lee JB, Lee JE, Park JH, Kim SJ, Kim MK, Roh SI, Yoon HS. …

The Bone Extracellular Matrix as an Ideal Milieu for Cancer Cell Metastases.

Bone is a preferential site for cancer metastases, including multiple myeloma, prostate, and breast cancers.The composition of bone, especially the extracellular matrix (ECM), make it an attractive site for cancer cell colonization and survival. The bone ECM is composed of living cells embedded within a matrix composed of both organic and inorganic components. Among the organic components, type I collagen provides the tensile strength of bone. Inorganic components, including hydroxyapatite crystals, are an integral component of bone and provide bone with its rigidity. Under normal circumstance

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… The hypoxic cancer secretome induces pre-metastatic bone lesions through lysyl oxidase Nature 2015 522 106 110 10.1038/nature14492 26017313 PMC4961239 79. Cawston T. Young D. …

A Review of Gaucher Disease Pathophysiology, Clinical Presentation and Treatments.

Gaucher disease (GD, ORPHA355) is a rare, autosomal recessive genetic disorder. It is caused by a deficiency of the lysosomal enzyme, glucocerebrosidase, which leads to an accumulation of its substrate, glucosylceramide, in macrophages. In the general population, its incidence is approximately 1/40,000 to 1/60,000 births, rising to 1/800 in Ashkenazi Jews. The main cause of the cytopenia, splenomegaly, hepatomegaly, and bone lesions associated with the disease is considered to be the infiltration of the bone marrow, spleen, and liver by Gaucher cells. Type-1 Gaucher disease, which affects the

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… Characterization of Gaucher disease bone marrow mesenchymal stromal cells reveals an altered inflammatory secretome. Blood. 2009;114:3181–3190. doi: 10.1182/blood-2009-02-205708. 26. …

Program-Abstracts

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… Lewis , London, ON, Canada Intravital Imaging of Human Prostate Cancer Using Bombesin-Targeted Viral Nanoparticles 11:54 Christopher Gerner , Vienna, Austria Novel Multiple Myeloma Biomarker Candidates Identified in the Secretome of Bone Marrow Fibroblasts and Endothelial Cells 12:06 Thomas Mohr …

Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition.

The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, and signaling molecules that interact to promote tumor growth and therapeutic resistance. Elucidating the intricate interactions between cancer cells and the TME is crucial in understanding cancer progression and therapeutic challenges. A critical process induced by TME signaling is the epithelial-mesenchymal transition (EMT), wherein epithelial cells acquire mesenchymal traits, which enhance their motility and inva

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… Their secretome, in addition to pro-inflammatory cytokines, angiogenic growth factors, and ECM, has strong impact on the formation, stabilization, and remodeling of vasculature. Their capacity for differentiation further contributes to vascular remodeling in different manners. … Their secretome, in addition to pro-inflammatory cytokines, angiogenic growth factors, and ECM, has strong impact on the formation, stabilization, and remodeling of vasculature. Their capacity for differentiation further contributes to vascular remodeling in different manners. …

The role of mesenchymal stem cells in attenuating inflammatory bowel disease through ubiquitination.

Inflammatory bowel disease (IBD), a condition of the digestive tract and one of the autoimmune diseases, is becoming a disease of significant global public health concern and substantial clinical burden. Various signaling pathways have been documented to modulate IBD, but the exact activation and regulatory mechanisms have not been fully clarified; thus, a need for constant exploration of the molecules and pathways that play key roles in the development of IBD. In recent years, several protein post-translational modification pathways, such as ubiquitination, phosphorylation, methylation, acety

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… Proteomic profiling reveals the ambivalent character of the mesenchymal stem cell secretome: assessing the effect of preconditioned media on isolated human islets. Cell Transplant. (2020) 29:963689720952332. doi: 10.1177/0963689720952332 60. Sun Y, Shi H, Yin S, Ji C, Zhang X, Zhang B, et al. …

Chemokine-Directed Tumor Microenvironment Modulation in Cancer Immunotherapy.

Chemokines are a large family of small chemotactic cytokines that coordinates immune cell trafficking. In cancer, they have a pivotal role in the migration pattern of immune cells into the tumor, thereby shaping the tumor microenvironment immune profile, often towards a pro-tumorigenic state. Furthermore, chemokines can directly target non-immune cells in the tumor microenvironment, including cancer, stromal and vascular endothelial cells. As such, chemokines participate in several cancer development processes such as angiogenesis, metastasis, cancer cell proliferation, stemness and invasivene

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… Oncogenic RAS -Induced Senescence in Human Primary Thyrocytes: Molecular Effectors and Inflammatory Secretome Involved. Oncotarget. 2014;5:8270–8283. doi: 10.18632/oncotarget.2013. 70. Salminen A., Kauppinen A., Kaarniranta K. …

Switching Homes: How Cancer Moves to Bone.

Bone metastases (BM) are a very common complication of the most prevalent human cancers. BM are extremely painful and may be life-threatening when associated with hypercalcaemia. BM can lead to kidney failure and cardiac arrhythmias and arrest, but why and how do cancer cells decide to "switch homes" and move to bone? In this review, we will present what answers science has provided so far, with focus on the molecular mechanisms and cellular aspects of well-established findings, such as the concept of "vicious cycle" and "osteolytic" vs. "osteosclerotic" bone metastases; as well as on novel co

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… The hypoxic cancer secretome induces pre-metastatic bone lesions through lysyl oxidase. Nature. 2015;522:106–110. doi: 10.1038/nature14492. 88. Kelly T., Suva L.J., Huang Y., MacLeod V., Miao H.Q., Walker R.C., Sanderson R.D. …

Osteoporosis in Frail Patients: A Consensus Paper of the Belgian Bone Club.

In this consensus paper, the Belgian Bone Club aims to provide a state of the art on the epidemiology, diagnosis, and management of osteoporosis in frail individuals, including patients with anorexia nervosa, patients on dialysis, cancer patients, persons with sarcopenia, and the oldest old. All these conditions may indeed induce bone loss that is superimposed on physiological bone loss and often remains under-recognized and under-treated. This is of particular concern because of the major burden of osteoporotic fractures in terms of morbidity, mortality, and economic cost. Therefore, there is

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… The muscle secretome consists of several hundred secreted peptides, providing a whole new paradigm for understanding how muscles communicate with other organs, including bones [ 63 ]. …

Postbiotics as Emerging Strategy Targeting Obesity- and Aging-Related Breast Cancer-Prospects in Prophylaxis and Therapy.

Aging and obesity accompanied with hormonal disequilibrium represent critical, inter-related risk factors for breast cancer, significantly influencing disease incidence, progression, and therapeutic outcomes. This review aims to elucidate the multifaceted biological mechanisms linking obesity and aging to breast carcinogenesis, with a particular focus on the emerging therapeutic and preventive potential of postbiotics as molecules targeting cellular events important for cancer growth and responsiveness. Despite continuous advancement, breast cancer therapy still poses several challenges, such

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… SASP secretome consists of several factors favoring tumor expansion, such as growth factors, matrix metalloproteinases, chemokines and pro-inflammatory cytokines. …

New genomic and proteomic biomarker discovery in cancer: revolutionizing diagnosis and prognostication.

Cancer remains a major global health challenge, with substantial morbidity and mortality worldwide. Advances in genomic and proteomic biomarker discovery have transformed cancer diagnosis, prognosis, and treatment selection. The evolution from early serological markers such as carcinoembryonic antigen (CEA) and prostate-specific antigen (PSA) to modern multi-omics approaches enabled by next-generation sequencing (NGS), mass spectrometry (MS), and advanced bioinformatics has revolutionized personalized medicine and targeted therapy, leading to improved outcomes. This review highlights the histo

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… Proteomic analysis of tumor secretomes and microenvironments has also revealed biomarkers like class III β-tubulin in ovarian cancer, predicting poor survival in neoadjuvant chemotherapy patients [ 31 ]. …

Sphingolipid metabolism and hematologic disorders: current understanding and future directions.

Sphingolipids are not only key structural components of cell membranes but also serve as important signaling molecules, and their metabolic homeostasis is essential for the maintenance of cellular functions. In recent years, with the advancement of technologies such as metabolomics, studies have revealed that sphingolipid metabolic abnormalities are extensively involved in the occurrence and development of various hematological disorders, including immune thrombocytopenia, myeloproliferative neoplasms, graft-versus-host disease, hereditary hematological diseases, and hematologic malignancies.

Influence of gut microbial metabolites on tumor immunotherapy: mechanisms and potential natural products.

In recent years, tumor immunotherapy has made significant breakthroughs in the treatment of malignant tumors. However, individual differences in efficacy have been observed in clinical practice. There is increasing evidence that gut microbial metabolites influence the efficacy of distal tumor immunotherapy via the gut-liver axis, the gut-brain axis and the gut-breast axis, a process that may involve modulating the expression of immune cells and cytokines in the tumor microenvironment (TME). In this review, we systematically explore the relationship between gut microbial metabolites and tumor i

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… Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome . Nature . ( 7456 ) 2013 499 : 97 – 101 . 10.1038/nature12347 23803760 101 Yamagishi R Kamachi F Nakamura M Yamazaki S Kamiya T Takasugi M . …