PMID- 33008082
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231112
IS  - 2310-2861 (Electronic)
IS  - 2310-2861 (Linking)
VI  - 6
IP  - 4
DP  - 2020 Sep 30
TI  - Matrix Remodeling and Hyaluronan Production by Myofibroblasts and 
      Cancer-Associated Fibroblasts in 3D Collagen Matrices.
LID - 10.3390/gels6040033 [doi]
LID - 33
AB  - The tumor microenvironment is a key modulator in cancer progression and has 
      become a novel target in cancer therapy. An increase in hyaluronan (HA) 
      accumulation and metabolism can be found in advancing tumor progression and are 
      often associated with aggressive malignancy, drug resistance and poor prognosis. 
      Wound-healing related myofibroblasts or activated cancer-associated fibroblasts 
      (CAF) are assumed to be the major sources of HA. Both cell types are capable to 
      synthesize new matrix components as well as reorganize the extracellular matrix. 
      However, to which extent myofibroblasts and CAF perform these actions are still 
      unclear. In this work, we investigated the matrix remodeling and HA production 
      potential in normal human dermal fibroblasts (NHFB) and CAF in the absence and 
      presence of transforming growth factor beta -1 (TGF-beta1), with TGF-beta1 being a 
      major factor of regulating fibroblast differentiation. Three-dimensional (3D) 
      collagen matrix was utilized to mimic the extracellular matrix of the tumor 
      microenvironment. We found that CAF appeared to response insensitively towards 
      TGF-beta1 in terms of cell proliferation and matrix remodeling when compared to 
      NHFB. In regards of HA production, we found that both cell types were capable to 
      produce matrix bound HA, rather than a soluble counterpart, in response to 
      TGF-beta1. However, activated CAF demonstrated higher HA production when compared to 
      myofibroblasts. The average molecular weight of produced HA was found in the 
      range of 480 kDa for both cells. By analyzing gene expression of HA metabolizing 
      enzymes, namely hyaluronan synthase (HAS1-3) and hyaluronidase (HYAL1-3) 
      isoforms, we found expression of specific isoforms in dependence of TGF-beta1 
      present in both cells. In addition, HAS2 and HYAL1 are highly expressed in CAF, 
      which might contribute to a higher production and degradation of HA in CAF 
      matrix. Overall, our results suggested a distinct behavior of NHFB and CAF in 3D 
      collagen matrices in the presence of TGF-beta1 in terms of matrix remodeling and HA 
      production pointing to a specific impact on tumor modulation.
FAU - Sapudom, Jiranuwat
AU  - Sapudom J
AUID- ORCID: 0000-0001-6627-7713
AD  - Laboratory for Immuno Bioengineering Research and Applications, Division of 
      Engineering, New York University Abu Dhabi, Abu Dhabi P.O. Box 129188, UAE.
AD  - Institute of Biochemistry, Faculty of Life Sciences, Universitat Leipzig, 04103 
      Leipzig, Germany.
AD  - Department of Dermatology, Venereology and Allergology, Faculty of Medicine, 
      Universitat Leipzig, 04103 Leipzig, Germany.
FAU - Muller, Claudia Damaris
AU  - Muller CD
AUID- ORCID: 0000-0002-3640-9815
AD  - Institute of Biochemistry, Faculty of Life Sciences, Universitat Leipzig, 04103 
      Leipzig, Germany.
FAU - Nguyen, Khiet-Tam
AU  - Nguyen KT
AUID- ORCID: 0000-0002-5884-9942
AD  - Department of Dermatology, Venereology and Allergology, Faculty of Medicine, 
      Universitat Leipzig, 04103 Leipzig, Germany.
FAU - Martin, Steve
AU  - Martin S
AD  - Institute of Biochemistry, Faculty of Life Sciences, Universitat Leipzig, 04103 
      Leipzig, Germany.
FAU - Anderegg, Ulf
AU  - Anderegg U
AUID- ORCID: 0000-0002-3993-9192
AD  - Department of Dermatology, Venereology and Allergology, Faculty of Medicine, 
      Universitat Leipzig, 04103 Leipzig, Germany.
FAU - Pompe, Tilo
AU  - Pompe T
AUID- ORCID: 0000-0003-1508-4959
AD  - Institute of Biochemistry, Faculty of Life Sciences, Universitat Leipzig, 04103 
      Leipzig, Germany.
LA  - eng
GR  - AN276/6-1/Deutsche Forschungsgemeinschaft/
GR  - PO713/9-1/Deutsche Forschungsgemeinschaft/
GR  - INST 268/293-1 FUGG/Deutsche Forschungsgemeinschaft/
GR  - 100146227/European Regional Development Fund/
PT  - Journal Article
DEP - 20200930
PL  - Switzerland
TA  - Gels
JT  - Gels (Basel, Switzerland)
JID - 101696925
PMC - PMC7709683
OTO - NOTNLM
OT  - cancer associated fibroblast
OT  - hyaluronan
OT  - matrix remodeling
OT  - myofibroblast
OT  - transforming growth factor beta 1
OT  - tumor microenvironment
COIS- The authors declare no conflict of interest.
EDAT- 2020/10/04 06:00
MHDA- 2020/10/04 06:01
PMCR- 2020/09/30
CRDT- 2020/10/03 01:01
PHST- 2020/08/25 00:00 [received]
PHST- 2020/09/14 00:00 [revised]
PHST- 2020/09/27 00:00 [accepted]
PHST- 2020/10/03 01:01 [entrez]
PHST- 2020/10/04 06:00 [pubmed]
PHST- 2020/10/04 06:01 [medline]
PHST- 2020/09/30 00:00 [pmc-release]
AID - gels6040033 [pii]
AID - gels-06-00033 [pii]
AID - 10.3390/gels6040033 [doi]
PST - epublish
SO  - Gels. 2020 Sep 30;6(4):33. doi: 10.3390/gels6040033.