Cancer Microenvironment

, Volume 8, Issue 1, pp 1–14 | Cite as

Tumor-driven Molecular Changes in Human Mesenchymal Stromal Cells

  • Lucia KucerovaEmail author
  • Jakub Zmajkovic
  • Lenka Toro
  • Svetlana Skolekova
  • Lucia Demkova
  • Miroslava Matuskova
Original Paper


Mesenchymal stromal cells (MSC) exert either tumor-stimulatory or tumor-inhibitory effect. The outcome of the tumor-MSC interaction is dictated by the tumor-specific activating signals. We analyzed the alterations in MSC phenotype in response to stimulation by tumor-secreted paracrine factors. Paracrine factors from human melanoma A375 and glioblastoma 8MGBA cells were used for prolonged culture of MSC to produce derived cells designated DIFF(A)-MSC or DIFF(G)-MSC, respectively. Derived cells were analyzed for the specific surface markers, the expression pattern of MSC markers and fibroblast-specific proteins. Changes in the cell phenotype were evaluated using scratch wound assay and tube formation in vitro; and xenotransplant growth in vivo. Our data show induced expression of vascular endothelial growth factor 2, CD146, fibroblast-specific protein, vimentin and endosialin in DIFF(A)-MSC cells. This indicates their differentiation towards the cells with features of tumor-associated fibroblasts upon stimulation with melanoma-secreted cytokines. Paracrine stimulation in DIFF(G)-MSC led to up-regulation of the genes involved in the MSC differentiation. MSC-specific surface marker characteristics were preserved in derived DIFF(A)-MSC and DIFF(G)-MSC cells. However, we observed increased proportion of CD146 and GD2 (neural ganglioside) positive cells and decreased expression of marker NG2 in the MSC exposed to tumor-conditioned medium. Melanoma-CM increased MSC migration, glioblastoma-CM compromised angiogenic capacity of MSC in vitro and the protumorigenic effect in vivo. Our data directly compare the pleiotropic effects mediated by the malignant cells on the MSC. Secreted paracrine factors from melanoma or glioblastoma differently changed molecular traits in MSC, which explains the dual role of MSC in tumor growth.


Human mesenchymal stromal cells Differentiation Melanoma Glioblastoma Tumor-associated fibroblasts 



Activated leukocyte cell adhesion molecule


α-smooth muscle actin


ATP-binding cassette, sub-family G, ABCG2


RANTES chemokine


Receptor for CCL5 (RANTES)


SCF receptor


CXCL10 receptor


SDF1α (CXCL12) receptor


Epidermal growth factor receptor


Enzyme-linked immunosorbent assay


Fibroblast-activating protein


Foetal bovine serum


Fibroblast specific protein


Glyceraldehyde 3-phosphate dehydrogenase


Granulocyte-colony stimulating factor


Neural ganglioside


Granulocyte monocyte-colony stimulating factor


Hepatocyte growth factor


Hypoxantine-guanine phosphoribosyl transferase


Interferon γ




Chemokine (C-X-C motif) ligand 10, CXCL10


Melanoma cell adhesion molecule, CD146

MCP-1 (CCL2)

Monocyte chemoattractant protein-1, chemokine CCL2

MIP-1a (CCL3)

Macrophage inflammatory protein-1alpha

MIP-1b (CCL4)

Macrophage inflammatory protein-1beta


mesenchymal stromal cells


Platelet-derived growth factor


Regulated on activation, normal T-cell expressed and secreted


Stem cell factor


Stroma-derived factor 1α, chemokine CXCL12


Tumor necrosis factor α


Tumor associated fibroblasts


Tumor cell-conditioned medium


Vascular cell adhesion molecule 1


Vascular endothelial growth factor


VEGF receptor



We acknowledge the excellent technical help and assistance from M. Dubrovcakova and V. Frivalska. We acknowledge K. Zmajkovicova, PhD, for the kind help with the confocal microscopy. This work was supported by the Slovak Research and Development Agency under the contract No. APVV-0230-11, APVV-0052-12, VEGA grants 2/0088/11 and 2/0171/13. The experiments on the CFX96™ Real-Time PCR Detection System and the IncuCyte ZOOM™ were enabled with the kind help and the financial support from the Cancer Research Foundation RFL2009 and RFL2012.

Conflict of Interest

The authors declare no conflict of interest.

Authors Contributions

Conception, design and development of methodology: LK, JZ; data acquisition LK, JZ, SS, LD, LB, MM; analysis and data interpretation LK, JZ, MM; writing of the manuscript and review: LK, JZ. All authors have read and approved the final version of the manuscript.

Supplementary material

12307_2014_151_MOESM1_ESM.docx (14 kb)
ESM 1 (DOCX 14 kb)


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Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Lucia Kucerova
    • 1
    Email author
  • Jakub Zmajkovic
    • 1
    • 2
  • Lenka Toro
    • 1
  • Svetlana Skolekova
    • 1
  • Lucia Demkova
    • 1
  • Miroslava Matuskova
    • 1
  1. 1.Laboratory of Molecular Oncology, Cancer Research InstituteSlovak Academy of SciencesBratislavaSlovakia
  2. 2.Arsanis Biosciences GmbHViennaAustria

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