Wessely, Anja and Waltera, Anna and Reichert, Torsten E. and Stoeckl, Sabine and Graessel, Susanne and Bauer, Richard J. (2019) Induction of ALP and MMP9 activity facilitates invasive behavior in heterogeneous human BMSC and HNSCC 3D spheroids. FASEB JOURNAL, 33 (11). pp. 11884-11893. ISSN 0892-6638, 1530-6860
Full text not available from this repository. (Request a copy)Abstract
Mesenchymal stem cells (MSCs) are multipotent progenitor cells capable of differentiating into adipocytic, osteogenic, chondrogenic, and myogenic lineages. There is growing evidence that MSCs home into the tumor microenvironment attracted by a variety of signals such as chemokines, growth factors, and cytokines. Tumor-homing stem cells may originate from bone marrow-derived MSCs (BMSCs) or adipose tissue-derived MSCs. Recent scientific data suggest that MSCs in combination with tumor cells can either promote or inhibit tumorigenic behavior. In head and neck squamous cell carcinoma (HNSCC), BMSCs are reported to be enriched with a potential negative role. Here, we evaluated the effect of BMSCs from 4 different donors in combination with 4 HNSCC cell lines in a 3-dimensional multicellular spheroid model. Heterogeneous combinations revealed an up-regulation of gene and protein expression of osteogenic markers runt-related transcription factor 2 (RUNX2) and alkaline phosphatase (ALP) together with a substantial secretion of matrix metalloproteinase 9. Moreover, heterogenous BMSC/tumor spheroids showed increased invasion compared with homogenous spheroids in a Boyden chamber invasion assay. Furthermore, inhibition of ALP resulted in a substantially decreased spreading of heterogeneous spheroids on laminin-rich matrix. In summary, our data suggest a prometastatic effect of BMSCs combined with HNSCC.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SQUAMOUS-CELL CARCINOMA; MESENCHYMAL STEM-CELLS; ALKALINE-PHOSPHATASE; BONE-MARROW; FACTOR RUNX2; CANCER; HEAD; TRANSCRIPTION; METASTASIS; EXPRESSION; mesenchymal stem cells; HNSCC; matrix-metalloproteinase; RUNX2; spheroid culture |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Mund-, Kiefer- und Gesichtschirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 24 Mar 2020 12:45 |
| Last Modified: | 24 Mar 2020 12:45 |
| URI: | https://pred.uni-regensburg.de/id/eprint/25877 |
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