Back
Increased PD-L1 expression and IL-6 secretion characterize human lung tumor-derived perivascular-like cells that promote vascular leakage in a perfusable microvasculature model.
Journal article

Increased PD-L1 expression and IL-6 secretion characterize human lung tumor-derived perivascular-like cells that promote vascular leakage in a perfusable microvasculature model.

  • Bichsel CA ARTORG Organs-on-Chip Technologies, University of Bern, Bern, Switzerland.
  • Wang L Department of BioMedical Research, University of Bern, Bern, Switzerland.
  • Froment L Department of BioMedical Research, University of Bern, Bern, Switzerland.
  • Berezowska S Department of Pathology, University of Bern, Bern, Switzerland.
  • Müller S Flow cytometry core facility, Department of BioMedical Research, University of Bern, Bern, Switzerland.
  • Dorn P Department of BioMedical Research, University of Bern, Bern, Switzerland.
  • Marti TM Department of BioMedical Research, University of Bern, Bern, Switzerland.
  • Peng RW Department of BioMedical Research, University of Bern, Bern, Switzerland.
  • Geiser T Department of Pulmonary Medicine, Inselspital, Bern University Hospital, Bern, Switzerland.
  • Schmid RA Department of BioMedical Research, University of Bern, Bern, Switzerland. Ralph.Schmid@insel.ch.
  • Guenat OT ARTORG Organs-on-Chip Technologies, University of Bern, Bern, Switzerland.
  • Hall SRR Department of BioMedical Research, University of Bern, Bern, Switzerland. Sean.Hall@insel.ch.
Show more…
  • 2017-09-08
Published in:
  • Scientific reports. - 2017
5'-Nucleotidase
B7-H1 Antigen
Biomarkers
Capillary Permeability
Carcinoma, Non-Small-Cell Lung
Epithelial Cell Adhesion Molecule
Humans
Interleukin-6
Lung Neoplasms
Mesenchymal Stem Cells
Microvessels
Neovascularization, Pathologic
Pericytes
Stromal Cells
Thy-1 Antigens
Transforming Growth Factor beta
English Pericytes represent important support cells surrounding microvessels found in solid organs. Emerging evidence points to their involvement in tumor progression and metastasis. Although reported to be present in the human lung, their specific presence and functional orientation within the tumor microenvironment in non-small cell lung cancer (NSCLC) has not yet been adequately studied. Using a multiparameter approach, we prospectively identified, sorted and expanded mesenchymal cells from human primary NSCLC samples based on co-expression of CD73 and CD90 while lacking hematopoietic and endothelial lineage markers (CD45, CD31, CD14 and Gly-A) and the epithelial marker EpCAM. Compared to their normal counterpart, tumor-derived Lineage-EpCAM-CD73+CD90+ cells showed enhanced expression of the immunosuppressive ligand PD-L1, a higher constitutive secretion of IL-6 and increased basal αSMA levels. In an in vitro model of 3D microvessels, both tumor-derived and matched normal Lineage-EpCAM-CD73+CD90+ cells supported the assembly of perfusable vessels. However, tumor-derived Lineage-EpCAM-CD73+CD90+ cells led to the formation of vessels with significantly increased permeability. Together, our data show that perivascular-like cells present in NSCLC retain functional abnormalities in vitro. Perivascular-like cells as an eventual target in NSCLC warrants further investigation.
Language
  • English
Open access status
gold
Identifiers
Persistent URL
https://sonar.ch/global/documents/278598
Statistics
Document views: 89 File downloads: