C-src enriched serum microvesicles are generated in malignant plasma cell dyscrasia.
Plasma cell dyscrasias are immunosecretory disorders that can lead to hematological malignancies such as Multiple Myeloma (MM). MM accounts for 15% of all hematologic cancers, and those diagnosed with MM typically become severely ill and have a low life expectancy. Monoclonal immunoglobulin Free Lig...
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oai:doaj.org-article:20e90398324446fb8f1217e345fe02262021-11-18T09:01:15ZC-src enriched serum microvesicles are generated in malignant plasma cell dyscrasia.1932-620310.1371/journal.pone.0070811https://doaj.org/article/20e90398324446fb8f1217e345fe02262013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23940647/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Plasma cell dyscrasias are immunosecretory disorders that can lead to hematological malignancies such as Multiple Myeloma (MM). MM accounts for 15% of all hematologic cancers, and those diagnosed with MM typically become severely ill and have a low life expectancy. Monoclonal immunoglobulin Free Light Chains (FLC) are present in the serum and urine of many patients with plasma cell diseases. The biological differences between monoclonal FLCs, produced under malignant or benign dyscrasias, has not yet been characterized. In the present study, we show that endothelial and heart muscle cell lines internalize kappa and lambda FLCs. After internalization, FLCs are rerouted in the extracellular space via microvesicles and exosomes that can be re-internalized in contiguous cells. Only FLCs secreted from malignant B Lymphocytes were carried in Hsp70, annexin V, and c-src positive vesicles. In both MM and AL Amyloidosis patients we observed an increase in microvesicle and exosome production. Isolated serum vesicles from MM, AL Amyloidosis and monoclonal gammopathy of undetermined significance (MGUS) patients contained FLCs. Furthermore MM and AL amyloidosis vesicles were strongly positive for Hsp70, annexin V, and c-src compared to MGUS and control patients. These are the first data implying that FLCs reroute via microvesicles in the blood stream, and also suggest a potential novel mechanism of c-src activation in plasma cell dyscrasia.Giuseppe Di NotoLucia PaoliniAndrea ZendriniAnnalisa RadeghieriLuigi CaimiDoris RicottaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 8, p e70811 (2013) |
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Medicine R Science Q Giuseppe Di Noto Lucia Paolini Andrea Zendrini Annalisa Radeghieri Luigi Caimi Doris Ricotta C-src enriched serum microvesicles are generated in malignant plasma cell dyscrasia. |
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Plasma cell dyscrasias are immunosecretory disorders that can lead to hematological malignancies such as Multiple Myeloma (MM). MM accounts for 15% of all hematologic cancers, and those diagnosed with MM typically become severely ill and have a low life expectancy. Monoclonal immunoglobulin Free Light Chains (FLC) are present in the serum and urine of many patients with plasma cell diseases. The biological differences between monoclonal FLCs, produced under malignant or benign dyscrasias, has not yet been characterized. In the present study, we show that endothelial and heart muscle cell lines internalize kappa and lambda FLCs. After internalization, FLCs are rerouted in the extracellular space via microvesicles and exosomes that can be re-internalized in contiguous cells. Only FLCs secreted from malignant B Lymphocytes were carried in Hsp70, annexin V, and c-src positive vesicles. In both MM and AL Amyloidosis patients we observed an increase in microvesicle and exosome production. Isolated serum vesicles from MM, AL Amyloidosis and monoclonal gammopathy of undetermined significance (MGUS) patients contained FLCs. Furthermore MM and AL amyloidosis vesicles were strongly positive for Hsp70, annexin V, and c-src compared to MGUS and control patients. These are the first data implying that FLCs reroute via microvesicles in the blood stream, and also suggest a potential novel mechanism of c-src activation in plasma cell dyscrasia. |
format |
article |
author |
Giuseppe Di Noto Lucia Paolini Andrea Zendrini Annalisa Radeghieri Luigi Caimi Doris Ricotta |
author_facet |
Giuseppe Di Noto Lucia Paolini Andrea Zendrini Annalisa Radeghieri Luigi Caimi Doris Ricotta |
author_sort |
Giuseppe Di Noto |
title |
C-src enriched serum microvesicles are generated in malignant plasma cell dyscrasia. |
title_short |
C-src enriched serum microvesicles are generated in malignant plasma cell dyscrasia. |
title_full |
C-src enriched serum microvesicles are generated in malignant plasma cell dyscrasia. |
title_fullStr |
C-src enriched serum microvesicles are generated in malignant plasma cell dyscrasia. |
title_full_unstemmed |
C-src enriched serum microvesicles are generated in malignant plasma cell dyscrasia. |
title_sort |
c-src enriched serum microvesicles are generated in malignant plasma cell dyscrasia. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2013 |
url |
https://doaj.org/article/20e90398324446fb8f1217e345fe0226 |
work_keys_str_mv |
AT giuseppedinoto csrcenrichedserummicrovesiclesaregeneratedinmalignantplasmacelldyscrasia AT luciapaolini csrcenrichedserummicrovesiclesaregeneratedinmalignantplasmacelldyscrasia AT andreazendrini csrcenrichedserummicrovesiclesaregeneratedinmalignantplasmacelldyscrasia AT annalisaradeghieri csrcenrichedserummicrovesiclesaregeneratedinmalignantplasmacelldyscrasia AT luigicaimi csrcenrichedserummicrovesiclesaregeneratedinmalignantplasmacelldyscrasia AT dorisricotta csrcenrichedserummicrovesiclesaregeneratedinmalignantplasmacelldyscrasia |
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1718421011010945024 |