Tumor cell behaviour modulation by mesenchymal stromal cells.
BACKGROUND
Human mesenchymal stromal cells (MSC) hold a promise for future cell-based therapies due to their immunomodulatory properties and/or secretory activity. Nevertheless non-neoplastic tumor compartment could also originate from MSC. We aimed to show whether multipotent MSC derived from human adipose tissue (AT-MSC) could create tumor cell-protective milieu and affect tumor cell behaviour in vitro and in vivo.


RESULTS
Here we have demonstrated tumor-promoting effect of AT-MSC on human melanoma A375 cells. AT-MSC coinjection mediated abrogation of tumor latency and supported subcutaneous xenotransplant growth from very low melanoma cell doses. Tumor incidence was also significantly increased by AT-MSC-derived soluble factors. AT-MSC supported proliferation, suppressed apoptosis and modulated melanoma cell responses to cytotoxic drugs in vitro. Expression and multiplex cytokine assays confirmed synergistic increase in VEGF that contributed to the AT-MSC-mediated support of A375 xenotransplant growth. Production of G-CSF and other factors implicated in formation of supportive proinflammatory tumor cell microenvironment was also confirmed. SDF-1alpha/CXCR4 signalling contributed to tumor-promoting effect of systemic AT-MSC administration on A375 xenotransplants. However, no support was observed for human glioblastoma cells 8MGBA co-injected along with AT-MSC that did not sustain tumor xenotransplant growth in vivo. Tumor-inhibiting response could be attributed to the synergistic action of multiple cytokines produced by AT-MSC on glioblastoma cells.


CONCLUSIONS
Herein we provide experimental evidence for MSC-mediated protective effect on melanoma A375 cells under nutrient-limiting and hostile environmental conditions resulting from mutual crosstalk between neoplastic and non-malignant cells. This tumor-favouring effect was not observed for the glioblastoma cells 8MGBA. Collectively, our data further strengthen the need for unravelling mechanisms underlying MSC-mediated modulation of tumor behaviour for possible future MSC clinical use in the context of malignant disease.
Laboratory of Molecular Oncology, Cancer Research Institute, Slovak Academy of Sciences, Bratislava, Slovakia. exonkuce@savba.sk
Lucia
L
Kucerova
Miroslava
M
Matuskova
Kristina
K
Hlubinova
Veronika
V
Altanerova
Cestmir
C
Altaner
D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D002450:Cell Communication / Q000502:physiology*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis*; D015870:Gene Expression; D020869:Gene Expression Profiling; D005909:Glioblastoma / Q000473:pathology; D006801:Humans; D008546:Melanoma, Experimental / Q000378:metabolism / Q000473:pathology*; D059630:Mesenchymal Stem Cells; D051379:Mice; D008819:Mice, Nude; D020239:Receptor Cross-Talk / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D023041:Xenograft Model Antitumor Assays
D016207:Cytokines