Multiple Myeloma Cell-Derived Secretome Modulates Bone Marrow Mesenchymal Stromal Cell Migration In Vitro
- 1i3S, Instituto de Investigação e Inovação em Saúde, , Rua Alfredo Allen, 208, 4200-135 Porto, Portugal
Abstract
Multiple myeloma (MM) depends on a permissive bone marrow microenvironment that supports malignant plasma cell survival and disease progression. Bone marrow mesenchymal stromal cells (BM-MSCs) are key components of this niche, but the mechanisms by which they are recruited by MM cells remain unclear. Here, we show that the MM-derived secretome (MM-Sec) promotes BM-MSC wound closure and transwell migration-associated responses in vitro. A small extracellular vesicle (sEV)-enriched pellet was isolated from MM.1S-Sec by differential ultracentrifugation and characterized, and the relative contributions of the sEV-enriched fraction and sEV-depleted secretome (post-100,000× g) to BM-MSC migration were assessed. The results show that the sEV-depleted secretome is more effective than the sEV-enriched fraction in promoting BM-MSC recruitment. Chemokine profiling of MM.1S-Sec identified CCL3 (MIP-1α) and CCL5 (RANTES) as abundant secreted factors and exploratory candidate contributors. Recombinant CCL3 and CCL5 increased the BM-MSC transwell migration response at high concentrations. Priming with MM.1S-Sec was associated with increased transwell migration-associated responses in the presence of CCL3 and CCL5. Together, these exploratory findings suggest that both vesicle-associated and soluble non-vesicular components may contribute to BM-MSC migration, while CCL3 and CCL5 may participate as candidate contributors within a broader network of soluble mediators. These findings identify secretome-mediated modulation of stromal migration as a relevant component of MM–microenvironment crosstalk that warrants further mechanistic investigation.
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BibTeX
@article{fernandes2026multiple,
title = {{Multiple Myeloma Cell-Derived Secretome Modulates Bone Marrow Mesenchymal Stromal Cell Migration In Vitro}},
author = {Maria João Fernandes and Andrea Giestinhas and Sara Reis Moura and Maria Helena Vasconcelos and Susana Gomes Santos and Maria José Oliveira and Maria Inês Almeida},
journal = {International journal of molecular sciences},
year = {2026},
month = sep,
doi = {10.3390/ijms27198763},
url = {https://europepmc.org/article/PMC/PMC13665306},
note = {CC BY},
}
RIS
TY - JOUR
TI - Multiple Myeloma Cell-Derived Secretome Modulates Bone Marrow Mesenchymal Stromal Cell Migration In Vitro
AU - Maria João Fernandes
AU - Andrea Giestinhas
AU - Sara Reis Moura
AU - Maria Helena Vasconcelos
AU - Susana Gomes Santos
AU - Maria José Oliveira
AU - Maria Inês Almeida
PY - 2026
DA - 2026/09/30
JO - International journal of molecular sciences
DO - 10.3390/ijms27198763
UR - https://europepmc.org/article/PMC/PMC13665306
AB - Multiple myeloma (MM) depends on a permissive bone marrow microenvironment that supports malignant plasma cell survival and disease progression. Bone marrow mesenchymal stromal cells (BM-MSCs) are key components of this niche, but the mechanisms by which they are recruited by MM cells remain unclear. Here, we show that the MM-derived secretome (MM-Sec) promotes BM-MSC wound closure and transwell migration-associated responses in vitro. A small extracellular vesicle (sEV)-enriched pellet was isolated from MM.1S-Sec by differential ultracentrifugation and characterized, and the relative contributions of the sEV-enriched fraction and sEV-depleted secretome (post-100,000× g) to BM-MSC migration were assessed. The results show that the sEV-depleted secretome is more effective than the sEV-enriched fraction in promoting BM-MSC recruitment. Chemokine profiling of MM.1S-Sec identified CCL3 (MIP-1α) and CCL5 (RANTES) as abundant secreted factors and exploratory candidate contributors. Recombinant CCL3 and CCL5 increased the BM-MSC transwell migration response at high concentrations. Priming with MM.1S-Sec was associated with increased transwell migration-associated responses in the presence of CCL3 and CCL5. Together, these exploratory findings suggest that both vesicle-associated and soluble non-vesicular components may contribute to BM-MSC migration, while CCL3 and CCL5 may participate as candidate contributors within a broader network of soluble mediators. These findings identify secretome-mediated modulation of stromal migration as a relevant component of MM–microenvironment crosstalk that warrants further mechanistic investigation.
SN - 1422-0067
ER -