Macrophages and mesenchymal stromal cells support survival and proliferation of multiple myeloma cells

Jaehyup Kim, Ryan A. Denu, Bridget A. Dollar, Leah E. Escalante, Justin P. Kuether, Natalie S. Callander, Fotis Asimakopoulos, Peiman Hematti

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Multiple myeloma (MM) is characterized by almost exclusive tropism of malignant cells for the bone marrow (BM) milieu. The survival and proliferation of malignant plasma cells have been shown to rely on interactions with nonmalignant stromal cells, in particular mesenchymal stromal cells (MSCs), in the BM microenvironment. However, the BM microenvironment is composed of a diverse array of cell types. This study examined the role of macrophages, an abundant component of BM stroma, as a potential niche component that supports malignant plasma cells. We investigated the proliferation of MM tumour cell lines when cultured alone or together with MSCs, macrophages, or a combination of MSCs and macrophages, using the carboxyfluorescein succinimidyl ester assay. Consistently, we observed increased proliferation of MM cell lines in the presence of either MSCs or macrophages compared to cell line-only control. Furthermore, the combined co-culture of MSCs plus macrophages induced the greatest degree of proliferation of myeloma cells. In addition to increased proliferation, MSCs and macrophages decreased the rate of apoptosis of myeloma cells. Our in vitro studies provide evidence that highlights the role of macrophages as a key component of the BM microenvironment facilitating the growth of malignant plasma cells in MM.

Original languageEnglish (US)
Pages (from-to)336-346
Number of pages11
JournalBritish Journal of Haematology
Volume158
Issue number3
DOIs
StatePublished - Aug 1 2012
Externally publishedYes

Fingerprint

Multiple Myeloma
Mesenchymal Stromal Cells
Cell Survival
Macrophages
Cell Proliferation
Plasma Cells
Bone Marrow
Cell Line
Tropism
Stromal Cells
Coculture Techniques
Tumor Cell Line
Bone Marrow Cells
Esters
Apoptosis
Growth

Keywords

  • Macrophages
  • Marrow stroma
  • Mesenchymal cells
  • Multiple myeloma
  • Myeloma

ASJC Scopus subject areas

  • Hematology

Cite this

Kim, J., Denu, R. A., Dollar, B. A., Escalante, L. E., Kuether, J. P., Callander, N. S., ... Hematti, P. (2012). Macrophages and mesenchymal stromal cells support survival and proliferation of multiple myeloma cells. British Journal of Haematology, 158(3), 336-346. https://doi.org/10.1111/j.1365-2141.2012.09154.x

Macrophages and mesenchymal stromal cells support survival and proliferation of multiple myeloma cells. / Kim, Jaehyup; Denu, Ryan A.; Dollar, Bridget A.; Escalante, Leah E.; Kuether, Justin P.; Callander, Natalie S.; Asimakopoulos, Fotis; Hematti, Peiman.

In: British Journal of Haematology, Vol. 158, No. 3, 01.08.2012, p. 336-346.

Research output: Contribution to journalArticle

Kim, J, Denu, RA, Dollar, BA, Escalante, LE, Kuether, JP, Callander, NS, Asimakopoulos, F & Hematti, P 2012, 'Macrophages and mesenchymal stromal cells support survival and proliferation of multiple myeloma cells', British Journal of Haematology, vol. 158, no. 3, pp. 336-346. https://doi.org/10.1111/j.1365-2141.2012.09154.x
Kim, Jaehyup ; Denu, Ryan A. ; Dollar, Bridget A. ; Escalante, Leah E. ; Kuether, Justin P. ; Callander, Natalie S. ; Asimakopoulos, Fotis ; Hematti, Peiman. / Macrophages and mesenchymal stromal cells support survival and proliferation of multiple myeloma cells. In: British Journal of Haematology. 2012 ; Vol. 158, No. 3. pp. 336-346.
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