Involvement of multiple myeloma cell-derived exosomes in osteoclast differentiation

Giacomo De Leo, Riccardo Alessandro, Simona Fontana, Simona Taverna, Samuele Raccosta, Odessa Schillaci, Riccardo Alessandro, Pierfrancesco Tassone, Gianluca Giavaresi, Lavinia Raimondi, Milena Fini, Daniele Bellavia, Nicola Amodio, Mauro Manno, Roberto Giardino, Samuele Raccosta, Angela De Luca, Alessandra Santoro

Risultato della ricerca: Article

62 Citazioni (Scopus)

Abstract

Bone disease is the most frequent complication in multiple myeloma (MM) resulting in osteolytic lesions, bone pain, hypercalcemia and renal failure. In MM bone disease the perfect balance between bone-resorbing osteoclasts (OCs) and bone-forming osteoblasts (OBs) activity is lost in favour of OCs, thus resulting in skeletal disorders. Since exosomes have been described for their functional role in cancer progression, we here investigate whether MM cell-derived exosomes may be involved in OCs differentiation. We show that MM cells produce exosomes which are actively internalized by Raw264.7 cell line, a cellular model of osteoclast formation. MM cell-derived exosomes positively modulate pre-osteoclast migration, through the increasing of CXCR4 expression and trigger a survival pathway. MM cell-derived exosomes play a significant pro-differentiative role in murine Raw264.7 cells and human primary osteoclasts, inducing the expression of osteoclast markers such as Cathepsin K (CTSK), Matrix Metalloproteinases 9 (MMP9) and Tartrate-resistant Acid Phosphatase (TRAP). Pre-osteoclast treated with MM cell-derived exosomes differentiate in multinuclear OCs able to excavate authentic resorption lacunae. Similar results were obtained with exosomes derived from MM patient's sera. Our data indicate that MM-exosomes modulate OCs function and differentiation. Further studies are needed to identify the OCs activating factors transported by MM cell-derived exosomes.
Lingua originaleEnglish
pagine (da-a)1-18
Numero di pagine18
RivistaOncotarget
Stato di pubblicazionePublished - 2015

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Exosomes
Osteoclasts
Multiple Myeloma
Bone Diseases
Bone and Bones
Cathepsin K
Matrix Metalloproteinase 9
Hypercalcemia
Osteoblasts
Renal Insufficiency

All Science Journal Classification (ASJC) codes

  • Oncology

Cita questo

Involvement of multiple myeloma cell-derived exosomes in osteoclast differentiation. / De Leo, Giacomo; Alessandro, Riccardo; Fontana, Simona; Taverna, Simona; Raccosta, Samuele; Schillaci, Odessa; Alessandro, Riccardo; Tassone, Pierfrancesco; Giavaresi, Gianluca; Raimondi, Lavinia; Fini, Milena; Bellavia, Daniele; Amodio, Nicola; Manno, Mauro; Giardino, Roberto; Raccosta, Samuele; De Luca, Angela; Santoro, Alessandra.

In: Oncotarget, 2015, pag. 1-18.

Risultato della ricerca: Article

De Leo, G, Alessandro, R, Fontana, S, Taverna, S, Raccosta, S, Schillaci, O, Alessandro, R, Tassone, P, Giavaresi, G, Raimondi, L, Fini, M, Bellavia, D, Amodio, N, Manno, M, Giardino, R, Raccosta, S, De Luca, A & Santoro, A 2015, 'Involvement of multiple myeloma cell-derived exosomes in osteoclast differentiation', Oncotarget, pagg. 1-18.
De Leo, Giacomo ; Alessandro, Riccardo ; Fontana, Simona ; Taverna, Simona ; Raccosta, Samuele ; Schillaci, Odessa ; Alessandro, Riccardo ; Tassone, Pierfrancesco ; Giavaresi, Gianluca ; Raimondi, Lavinia ; Fini, Milena ; Bellavia, Daniele ; Amodio, Nicola ; Manno, Mauro ; Giardino, Roberto ; Raccosta, Samuele ; De Luca, Angela ; Santoro, Alessandra. / Involvement of multiple myeloma cell-derived exosomes in osteoclast differentiation. In: Oncotarget. 2015 ; pagg. 1-18.
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abstract = "Bone disease is the most frequent complication in multiple myeloma (MM) resulting in osteolytic lesions, bone pain, hypercalcemia and renal failure. In MM bone disease the perfect balance between bone-resorbing osteoclasts (OCs) and bone-forming osteoblasts (OBs) activity is lost in favour of OCs, thus resulting in skeletal disorders. Since exosomes have been described for their functional role in cancer progression, we here investigate whether MM cell-derived exosomes may be involved in OCs differentiation. We show that MM cells produce exosomes which are actively internalized by Raw264.7 cell line, a cellular model of osteoclast formation. MM cell-derived exosomes positively modulate pre-osteoclast migration, through the increasing of CXCR4 expression and trigger a survival pathway. MM cell-derived exosomes play a significant pro-differentiative role in murine Raw264.7 cells and human primary osteoclasts, inducing the expression of osteoclast markers such as Cathepsin K (CTSK), Matrix Metalloproteinases 9 (MMP9) and Tartrate-resistant Acid Phosphatase (TRAP). Pre-osteoclast treated with MM cell-derived exosomes differentiate in multinuclear OCs able to excavate authentic resorption lacunae. Similar results were obtained with exosomes derived from MM patient's sera. Our data indicate that MM-exosomes modulate OCs function and differentiation. Further studies are needed to identify the OCs activating factors transported by MM cell-derived exosomes.",
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T1 - Involvement of multiple myeloma cell-derived exosomes in osteoclast differentiation

AU - De Leo, Giacomo

AU - Alessandro, Riccardo

AU - Fontana, Simona

AU - Taverna, Simona

AU - Raccosta, Samuele

AU - Schillaci, Odessa

AU - Alessandro, Riccardo

AU - Tassone, Pierfrancesco

AU - Giavaresi, Gianluca

AU - Raimondi, Lavinia

AU - Fini, Milena

AU - Bellavia, Daniele

AU - Amodio, Nicola

AU - Manno, Mauro

AU - Giardino, Roberto

AU - Raccosta, Samuele

AU - De Luca, Angela

AU - Santoro, Alessandra

PY - 2015

Y1 - 2015

N2 - Bone disease is the most frequent complication in multiple myeloma (MM) resulting in osteolytic lesions, bone pain, hypercalcemia and renal failure. In MM bone disease the perfect balance between bone-resorbing osteoclasts (OCs) and bone-forming osteoblasts (OBs) activity is lost in favour of OCs, thus resulting in skeletal disorders. Since exosomes have been described for their functional role in cancer progression, we here investigate whether MM cell-derived exosomes may be involved in OCs differentiation. We show that MM cells produce exosomes which are actively internalized by Raw264.7 cell line, a cellular model of osteoclast formation. MM cell-derived exosomes positively modulate pre-osteoclast migration, through the increasing of CXCR4 expression and trigger a survival pathway. MM cell-derived exosomes play a significant pro-differentiative role in murine Raw264.7 cells and human primary osteoclasts, inducing the expression of osteoclast markers such as Cathepsin K (CTSK), Matrix Metalloproteinases 9 (MMP9) and Tartrate-resistant Acid Phosphatase (TRAP). Pre-osteoclast treated with MM cell-derived exosomes differentiate in multinuclear OCs able to excavate authentic resorption lacunae. Similar results were obtained with exosomes derived from MM patient's sera. Our data indicate that MM-exosomes modulate OCs function and differentiation. Further studies are needed to identify the OCs activating factors transported by MM cell-derived exosomes.

AB - Bone disease is the most frequent complication in multiple myeloma (MM) resulting in osteolytic lesions, bone pain, hypercalcemia and renal failure. In MM bone disease the perfect balance between bone-resorbing osteoclasts (OCs) and bone-forming osteoblasts (OBs) activity is lost in favour of OCs, thus resulting in skeletal disorders. Since exosomes have been described for their functional role in cancer progression, we here investigate whether MM cell-derived exosomes may be involved in OCs differentiation. We show that MM cells produce exosomes which are actively internalized by Raw264.7 cell line, a cellular model of osteoclast formation. MM cell-derived exosomes positively modulate pre-osteoclast migration, through the increasing of CXCR4 expression and trigger a survival pathway. MM cell-derived exosomes play a significant pro-differentiative role in murine Raw264.7 cells and human primary osteoclasts, inducing the expression of osteoclast markers such as Cathepsin K (CTSK), Matrix Metalloproteinases 9 (MMP9) and Tartrate-resistant Acid Phosphatase (TRAP). Pre-osteoclast treated with MM cell-derived exosomes differentiate in multinuclear OCs able to excavate authentic resorption lacunae. Similar results were obtained with exosomes derived from MM patient's sera. Our data indicate that MM-exosomes modulate OCs function and differentiation. Further studies are needed to identify the OCs activating factors transported by MM cell-derived exosomes.

KW - Exosomes, Multiple Myeloma; Osteoclasts; Bone Formation

UR - http://hdl.handle.net/10447/126733

M3 - Article

SP - 1

EP - 18

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

ER -