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. 2014 Aug 12;5(4):95.
doi: 10.1186/scrt484.

The bidirectional tumor--mesenchymal stromal cell interaction promotes the progression of head and neck cancer

Benjamin A Kansy, Philip A Dißmann, Hatim Hemeda, Kirsten Bruderek, Anna M Westerkamp, Vivien Jagalski, Patrick Schuler, Katinka Kansy, Stephan Lang, Claudia A Dumitru, Sven Brandau

The bidirectional tumor--mesenchymal stromal cell interaction promotes the progression of head and neck cancer

Benjamin A Kansy et al. Stem Cell Res Ther. .

Abstract

Introduction: Mesenchymal stromal cells (MSC) are an integral cellular component of the tumor microenvironment. Nevertheless, very little is known about MSC originating from human malignant tissue and modulation of these cells by tumor-derived factors. The aim of this study was to isolate and characterize MSC from head and neck squamous cell carcinoma (HNSCC) and to investigate their interaction with tumor cells.

Methods: MSC were isolated from tumor tissues of HNSCC patients during routine oncological surgery. Immunophenotyping, immunofluorescence and in vitro differentiation were performed to determine whether the isolated cells met the consensus criteria for MSC. The cytokine profile of tumor-derived MSC was determined by enzyme-linked immunosorbent assay (ELISA). Activation of MSC by tumor-conditioned media was assessed by measuring cytokine release and expression of CD54. The impact of MSC on tumor growth in vivo was analyzed in a HNSCC xenograft model.

Results: Cells isolated from HNSCC tissue met the consensus criteria for MSC. Tumor-derived MSC constitutively produced high amounts of interleukin (IL)-6, IL-8 and stromal cell-derived factor (SDF)-1α. HNSCC-derived factors activated MSC and enhanced secretion of IL-8 and expression of CD54. Furthermore, MSC provided stromal support for human HNSCC cell lines in vivo and enhanced their growth in a murine xenograft model.

Conclusions: This is the first study to isolate and characterize MSC from malignant tissues of patients with HNSCC. We observed cross-talk of stromal cells and tumor cells resulting in enhanced growth of HNSCC in vivo.

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Figures

Figure 1
Figure 1
Immunophenotyping of head and neck squamous cell carcinoma-derived mesenchymal stromal cells. Mesenchymal stromal cells (MSC) were isolated from malignant tissue of patients with head and neck squamous cell carcinoma and were expanded. (a) Immunophenotyping was performed by flow cytometry. Data depicted as histograms. (b) Tumor-derived MSC were seeded on cover slips and immunofluorescence staining for vimentin and S100A4 was performed. Data and images from one representative experiment are shown.
Figure 2
Figure 2
Trilineage differentiation of head and neck squamous cell carcinoma-derived mesenchymal stromal cells. Tumor-derived mesenchymal stromal cells were harvested and subjected to trilineage differentiation using standard differentiation-inducing culture conditions. Top row: adipogenic differentiation after 14 days, staining performed with Sudan III. Middle row: chondrogenic differentiation after 14 days, staining with Alcian blue. Bottom row: osteogenic differentiation after 21 days, staining with Alizarin red. Images from one representative donor are shown.
Figure 3
Figure 3
Cytokine profile of tumor-derived mesenchymal stromal cells. Tumor-derived mesenchymal stromal cells obtained from three individual patients were cultured for 24 hours and the culture supernatant was harvested. Concentration of cytokines was analyzed with a bead-based multiplex assay. Secretion was classified as no secretion (IL-5, IL-7, IL-10, IL-12, IL-13, IL-17; data not shown), (a) low secretion (<100 pg/ml) and (b) high secretion (>100 pg/ml). Data depicted as mean ± standard deviation. G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte–macrophage colony-stimulating factor; IFN, interferon; IL, interleukin; MIP-1 β, macrophage inflammatory protein-1β; SDF-1α, stromal cell-derived factor-1α; TNFα, tumor necrosis factor alpha; VCAM1, vascular cell adhesion molecule 1.
Figure 4
Figure 4
Activation of tumor-derived mesenchymal stromal cells by head and neck squamous cell carcinoma-conditioned medium. Individual tumor-derived mesenchymal stromal cell (TuMSC) lines were incubated in the presence of culture supernatants obtained from head and neck squamous cell carcinoma cell lines. After 36 to 48 hours, the FaDu/UM22B conditioned supernatant was aspirated and replaced by fresh standard culture medium. After another 24 hours, the TuMSC culture supernatant (a) or TuMSC (b) was collected. Concentration of interleukin (IL)-8 was measured by enzyme-linked immunosorbent assay (a) and expression of CD54 on activated TuMSC was analyzed by flow cytometry (b, c). The experiment was performed with TuMSC from seven independent donors designated #1 to #7. APC, Allophycocyanin; MFI, median fluorescence intensity; SN, supernatant.
Figure 5
Figure 5
Effect of mesenchymal stromal cells on head and neck squamous cell carcinoma progression in a xenograft murine model. Equal numbers of mesenchymal stromal cells isolated from three different patient samples were pooled and admixed to HNSCC FaDu cells in a 1:1 ratio. Mixtures of tumor-derived mesenchymal stromal cells (TuMSC)–FaDu cells (n = 8) and bone marrow-derived mesenchymal stromal cells (BMMSC)–FaDu cells (n = 4) were injected into the right flank of immunodeficient nude mice. The control group was injected with only FaDu cells (n = 8). (a) The tumor volume was monitored by caliper measurements. Gray vertical line, sacrifice of mice according to ethic requirements. Cryosection slides of excised tumors (n = 3 for each group) were analyzed for Ki-67 staining (b) and apoptosis TUNEL staining (c). Representative pictures were chosen and analyzed under a 400-fold magnification. p.i., post injection (of tumor); TUNEL, terminal deoxynucleotidyl transferase-dUTP nick end-labeling.
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References

    1. Horwitz EM, Le Blanc K, Dominici M, Mueller I, Slaper-Cortenbach I, Marini FC, Deans RJ, Krause DS, Keating A. Clarification of the nomenclature for MSC: the International Society for Cellular Therapy position statement. Cytotherapy. 2005;7:393–395. doi: 10.1080/14653240500319234. - DOI - PubMed
    1. Hass R, Kasper C, Bohm S, Jacobs R. Different populations and sources of human mesenchymal stem cells (MSC): a comparison of adult and neonatal tissue-derived MSC. Cell Commun Signal. 2011;9:12. doi: 10.1186/1478-811X-9-12. - DOI - PMC - PubMed
    1. Miao Z, Jin J, Chen L, Zhu J, Huang W, Zhao J, Qian H, Zhang X. Isolation of mesenchymal stem cells from human placenta: comparison with human bone marrow mesenchymal stem cells. Cell Biol Int. 2006;30:681–687. doi: 10.1016/j.cellbi.2006.03.009. - DOI - PubMed
    1. Nathan S, Das De S, Thambyah A, Fen C, Goh J, Lee EH. Cell-based therapy in the repair of osteochondral defects: a novel use for adipose tissue. Tissue Eng. 2003;9:733–744. doi: 10.1089/107632703768247412. - DOI - PubMed
    1. Prockop DJ, Gregory CA, Spees JL. One strategy for cell and gene therapy: harnessing the power of adult stem cells to repair tissues. Proc Natl Acad Sci U S A. 2003;100:11917–11923. doi: 10.1073/pnas.1834138100. - DOI - PMC - PubMed

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