PMID- 36674806
OWN - NLM
STAT- MEDLINE
DCOM- 20230127
LR  - 20230201
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 24
IP  - 2
DP  - 2023 Jan 9
TI  - Opposing MMP-9 Expression in Mesenchymal Stromal Cells and Head and Neck Tumor 
      Cells after Direct 2D and 3D Co-Culture.
LID - 10.3390/ijms24021293 [doi]
LID - 1293
AB  - 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.
FAU - Waltera, Anna
AU  - Waltera A
AD  - Department of Oral and Maxillofacial Surgery, University Hospital Regensburg, 
      93053 Regensburg, Germany.
AD  - Department of Oral and Maxillofacial Surgery, Center for Medical Biotechnology, 
      University Hospital Regensburg, 93053 Regensburg, Germany.
FAU - Schulz, Daniela
AU  - Schulz D
AD  - Department of Oral and Maxillofacial Surgery, University Hospital Regensburg, 
      93053 Regensburg, Germany.
AD  - Department of Oral and Maxillofacial Surgery, Center for Medical Biotechnology, 
      University Hospital Regensburg, 93053 Regensburg, Germany.
FAU - Schaefer, Nicole
AU  - Schaefer N
AD  - Experimental Orthopaedics, Centre for Medical Biotechnology (ZMB), Bio Park 1, 
      University of Regensburg, 93053 Regensburg, Germany.
FAU - Stoeckl, Sabine
AU  - Stoeckl S
AD  - Experimental Orthopaedics, Centre for Medical Biotechnology (ZMB), Bio Park 1, 
      University of Regensburg, 93053 Regensburg, Germany.
FAU - Pion, Eric
AU  - Pion E
AD  - Institute for Molecular and Cellular Anatomy, University of Regensburg, 93053 
      Regensburg, Germany.
FAU - Haerteis, Silke
AU  - Haerteis S
AUID- ORCID: 0000-0002-9440-3307
AD  - Institute for Molecular and Cellular Anatomy, University of Regensburg, 93053 
      Regensburg, Germany.
FAU - Reichert, Torsten E
AU  - Reichert TE
AD  - Department of Oral and Maxillofacial Surgery, University Hospital Regensburg, 
      93053 Regensburg, Germany.
FAU - Ettl, Tobias
AU  - Ettl T
AD  - Department of Oral and Maxillofacial Surgery, University Hospital Regensburg, 
      93053 Regensburg, Germany.
FAU - Bauer, Richard J
AU  - Bauer RJ
AD  - Department of Oral and Maxillofacial Surgery, University Hospital Regensburg, 
      93053 Regensburg, Germany.
AD  - Department of Oral and Maxillofacial Surgery, Center for Medical Biotechnology, 
      University Hospital Regensburg, 93053 Regensburg, Germany.
LA  - eng
PT  - Journal Article
DEP - 20230109
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Humans
MH  - Bone Marrow Cells
MH  - *Coculture Techniques
MH  - *Head and Neck Neoplasms/genetics/metabolism
MH  - *Matrix Metalloproteinase 9/genetics/metabolism
MH  - *Mesenchymal Stem Cells/metabolism
MH  - Squamous Cell Carcinoma of Head and Neck/metabolism
MH  - Stromal Cells
MH  - Tumor Microenvironment
PMC - PMC9861345
OTO - NOTNLM
OT  - 3D
OT  - BMSC
OT  - CAM
OT  - HNSCC
OT  - MMP
OT  - angiogenesis
OT  - bone marrow-derived stromal cells
OT  - chorioallantoic membrane
OT  - head and neck cancer
OT  - in ovo, 2D
OT  - matrix metalloproteinase
COIS- The authors declare no conflict of interest.
EDAT- 2023/01/22 06:00
MHDA- 2023/01/25 06:00
PMCR- 2023/01/09
CRDT- 2023/01/21 01:26
PHST- 2022/11/28 00:00 [received]
PHST- 2022/12/23 00:00 [revised]
PHST- 2023/01/07 00:00 [accepted]
PHST- 2023/01/21 01:26 [entrez]
PHST- 2023/01/22 06:00 [pubmed]
PHST- 2023/01/25 06:00 [medline]
PHST- 2023/01/09 00:00 [pmc-release]
AID - ijms24021293 [pii]
AID - ijms-24-01293 [pii]
AID - 10.3390/ijms24021293 [doi]
PST - epublish
SO  - Int J Mol Sci. 2023 Jan 9;24(2):1293. doi: 10.3390/ijms24021293.