Multiple myeloma cell lines and primary tumors proteome: protein biosynthesis and Immune system as potential therapeutic targets

Fernando, Rodrigo Carlini; Carvalho, Flávio; Mazzotti, Diego R.; Evangelista, Adriane Feijó; Braga, Walter Moisés Tobias; Chauffaille, Maria de Lourdes Lopes Ferrari; Leme, Adriana Franco Paes; Colleoni, Gisele Wally Braga

doi:10.18632/genesandcancer.88

Cited by 17 publications

(15 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We also identified seven biological pathways from the KEGG database significantly overrepresented ( Figure 3B), in line with the GO biological processes, with emphasis on the following pathways: "protein processing in endoplasmic reticulum" and "ribosome" (both related to protein biosynthesis), and "oxidative phosphorylation", "fatty acid degradation", and "metabolism pathways "(all of them related to energy metabolism). In addition, we also identified an overlap of 24 upregulated DEP proteins from this study, compared to the data from our 2015 study (19), where we evaluated the protein expression of tumor plasma cells versus plasma cells from healthy donors ( Figure 5).…”

Section: Mm-mc Cd138-cd105vs Hd-mc Cd138-cd105-mentioning

confidence: 82%

“…High throughput techniques, such as mass spectrometry, microarray, RNA-seq, among others, allow the generation of an abundant amount of data, allowing to compare patient cells in pathological conditions, such as MM, in relation to cells derived from HD. In 2015, our group published a proteomics study in which we evaluated the protein expression of tumor plasma cells from MM patients in comparison to plasma cells from palatal tonsils from normal individuals ( 19 ). In this study, we identified 81 DEP among these cells (72 upregulated and nine downregulated).…”

Section: Discussionmentioning

confidence: 99%

“…Firstly, plasma cells were sorted by Magnetic-Activated Cell Sorting (MACS) methodology, using CD138 + as a positive marker (Miltenyi Biotec, Bergisch Gladbach, DEU). These cells were analyzed in another study from our group ( 19 ). Then, MSC were isolated, using CD105 + as a positive marker.…”

Section: Casuistic and Methodsmentioning

confidence: 99%

“…Venn diagram showing the overlap between the upregulated DEP in the current study (MM-MC CD138-CD105vs. HD-MC CD138-CD105-) compared to the upregulated DEP in our previous study (MM Plasma cells vs. HD Plasma cells) by Fernando et al(19). (A) Fernando et al(19) study; (B) Current study.…”

mentioning

confidence: 88%

See 3 more Smart Citations

Tumor Microenvironment Proteomics: Lessons From Multiple Myeloma

et al. 2021

Self Cite

View full text Add to dashboard Cite

Although the “seed and soil” hypothesis was proposed by Stephen Paget at the end of the 19th century, where he postulated that tumor cells (seeds) need a propitious medium (soil) to be able to establish metastases, only recently the tumor microenvironment started to be more studied in the field of Oncology. Multiple myeloma (MM), a malignancy of plasma cells, can be considered one of the types of cancers where there is more evidence in the literature of the central role that the bone marrow (BM) microenvironment plays, contributing to proliferation, survival, migration, and drug resistance of tumor cells. Despite all advances in the therapeutic arsenal for MM treatment in the last years, the disease remains incurable. Thus, studies aiming a better understanding of the pathophysiology of the disease, as well as searching for new therapeutic targets are necessary and welcome. Therefore, the present study aimed to evaluate the protein expression profiling of mononuclear cells derived from BM of MM patients in comparison with these same cell types derived from healthy individuals, in order to fill this gap in MM treatment. Proteomic analysis was performed using the mass spectrometry technique and further analyses were done using bioinformatics tools, to identify dysregulated biological pathways and/or processes in the BM microenvironment of patients with MM as a result of the disease. Among the pathways identified in this study, we can highlight an upregulation of proteins related to protein biosynthesis, especially chaperone proteins, in patients with MM. Additionally, we also found an upregulation of several proteins involved in energy metabolism, which is one of the cancer hallmarks. Finally, with regard to the downregulated proteins, we can highlight mainly those involved in different pathways of the immune response, corroborating the data that has demonstrated that the immune system of MM is impaired and, therefore, the immunotherapies that have been studied recently for the treatment of the disease are extremely necessary in the search for a control and a cure for these patients who live with the disease.

show abstract

Section: Mm-mc Cd138-cd105vs Hd-mc Cd138-cd105-mentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Casuistic and Methodsmentioning

confidence: 99%

mentioning

confidence: 88%

See 2 more Smart Citations

Tumor Microenvironment Proteomics: Lessons From Multiple Myeloma

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…To date, efforts to define the cell surface proteome of MM have focused on individual cell lines, 16 17 have studied changes in response to one particular therapy, 18 or have used methods that are not optimal for detection of low abundance membrane proteins. 19 As a result, knowledge of clinically informative MM cell surface proteins is lacking. In this study, we first used CSC to define the cell surface N-glycoproteome of four MM cell lines.…”

Section: Introductionmentioning

confidence: 99%

Discovery and validation of surfaceN-glycoproteins in MM cell lines and patient samples uncovers immunotherapy targets

Oldham

Faber

Keppel

et al. 2020

J Immunother Cancer

View full text Add to dashboard Cite

BackgroundMultiple myeloma (MM) is characterized by clonal expansion of malignant plasma cells in the bone marrow. While recent advances in treatment for MM have improved patient outcomes, the 5-year survival rate remains ~50%. A better understanding of the MM cell surface proteome could facilitate development of new directed therapies and assist in stratification and monitoring of patient outcomes.MethodsIn this study, we first used a mass spectrometry (MS)-based discovery-driven cell surface capture (CSC) approach to map the cell surface N-glycoproteome of MM cell lines. Next, we developed targeted MS assays, and applied these to cell lines and primary patient samples to refine the list of candidate tumor markers. Candidates of interest detected by MS on MM patient samples were further validated using flow cytometry (FCM).ResultsWe identified 696 MM cell surface N-glycoproteins by CSC, and developed 73 targeted MS detection assays. MS-based validation using primary specimens detected 30 proteins with significantly higher abundance in patient MM cells than controls. Nine of these proteins were identified as potential immunotherapeutic targets, including five that were validated by FCM, confirming their expression on the cell surface of primary MM patient cells.ConclusionsThis MM surface N-glycoproteome will be a valuable resource in the development of biomarkers and therapeutics. Further, we anticipate that our targeted MS assays will have clinical benefit for the diagnosis, stratification, and treatment of MM patients.

show abstract