Waltera, Anna and Schulz, Daniela and Schaefer, Nicole and Stoeckl, Sabine and Pion, Eric and Haerteis, Silke and Reichert, Torsten E. and Ettl, Tobias and Bauer, Richard J. (2023) Opposing MMP-9 Expression in Mesenchymal Stromal Cells and Head and Neck Tumor Cells after Direct 2D and 3D Co-Culture. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 24 (2): 1293. ISSN 1661-6596, 1422-0067
Full text not available from this repository. (Request a copy)Abstract
Bone marrow-derived mesenchymal stromal cells (BMSCs) respond to a variety of tumor cell-derived signals, such as inflammatory cytokines and growth factors. As a result, the inflammatory tumor microenvironment may lead to the recruitment of BMSCs. Whether BMSCs in the tumor environment are more likely to promote tumor growth or tumor suppression is still controversial. In our experiments, direct 3D co-culture of BMSCs with tumor cells from the head and neck region (HNSCC) results in strong expression and secretion of MMP-9. The observed MMP-9 secretion mainly originates from BMSCs, leading to increased invasiveness. In addition to our in vitro data, we show in vivo data based on the chorioallantoic membrane (CAM) model. Our results demonstrate that MMP-9 induces hemorrhage and increased perfusion in BMSC/HNSCC co-culture. While we had previously outlined that MMP-9 expression and secretion originate from BMSCs, our data showed a strong downregulation of MMP-9 promoter activity in HNSCC cells upon direct contact with BMSCs using the luciferase activity assay. Interestingly, the 2D and 3D models of direct co-culture suggest different drivers for the downregulation of MMP-9 promoter activity. Whereas the 3D model depicts a BMSC-dependent downregulation, the 2D model shows cell density-dependent downregulation. In summary, our data suggest that the direct interaction of HNSCC cells and BMSCs promotes tumor progression by significantly facilitating angiogenesis via MMP-9 expression. On the other hand, data from 3D and 2D co-culture models indicate opposing regulation of the MMP-9 promoter in tumor cells once stromal cells are involved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CHORIOALLANTOIC MEMBRANE CAM; STEM-CELLS; INTRACEREBRAL HEMORRHAGE; CANCER PROGRESSION; MATRIX METALLOPROTEINASES; CARCINOMA-CELLS; MATRIX-METALLOPROTEINASE-9; INVASION; GROWTH; MIGRATION; HNSCC; head and neck cancer; BMSC; bone marrow-derived stromal cells; angiogenesis; MMP; matrix metalloproteinase; CAM; chorioallantoic membrane; in ovo; 2D; 3D |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Mund-, Kiefer- und Gesichtschirurgie Biology, Preclinical Medicine > Institut für Anatomie > Lehrstuhl für Molekulare und zelluläre Anatomie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 08 Mar 2024 08:43 |
| Last Modified: | 08 Mar 2024 08:43 |
| URI: | https://pred.uni-regensburg.de/id/eprint/59041 |
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