PMID- 33809984
OWN - NLM
STAT- MEDLINE
DCOM- 20210430
LR  - 20210430
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 6
DP  - 2021 Mar 22
TI  - Cleavage of the Perlecan-Semaphorin 3A-Plexin A1-Neuropilin-1 (PSPN) Complex by 
      Matrix Metalloproteinase 7/Matrilysin Triggers Prostate Cancer Cell Dyscohesion 
      and Migration.
LID - 10.3390/ijms22063218 [doi]
LID - 3218
AB  - The Perlecan-Semaphorin 3A-Plexin A1-Neuropilin-1 (PSPN) Complex at the cell 
      surface of prostate cancer (PCa) cells influences cell-cell cohesion and 
      dyscohesion. We investigated matrix metalloproteinase-7/matrilysin (MMP-7)'s 
      ability to digest components of the PSPN Complex in bone metastatic PCa cells 
      using in silico analyses and in vitro experiments. Results demonstrated that in 
      addition to the heparan sulfate proteoglycan, perlecan, all components of the 
      PSPN Complex were degraded by MMP-7. To investigate the functional consequences 
      of PSPN Complex cleavage, we developed a preformed microtumor model to examine 
      initiation of cell dispersion after MMP-7 digestion. We found that while perlecan 
      fully decorated with glycosaminoglycan limited dispersion of PCa microtumors, 
      MMP-7 initiated rapid dyscohesion and migration even with perlecan present. 
      Additionally, we found that a bioactive peptide (PLN4) found in perlecan domain 
      IV in a region subject to digestion by MMP-7 further enhanced cell dispersion 
      along with MMP-7. We found that digestion of the PSPN Complex with MMP-7 
      destabilized cell-cell junctions in microtumors evidenced by loss of 
      co-registration of E-cadherin and F-actin. We conclude that MMP-7 plays a key 
      functional role in PCa cell transition from a cohesive, indolent phenotype to a 
      dyscohesive, migratory phenotype favoring production of circulating tumor cells 
      and metastasis to bone.
FAU - Tellman, Tristen V
AU  - Tellman TV
AD  - Department of Diagnostic and Biomedical Sciences, School of Dentistry, The 
      University of Texas Health Science Center at Houston, 7500 Cambridge Street Room 
      4401, Houston, TX 77054, USA.
FAU - Cruz, Lissette A
AU  - Cruz LA
AD  - Department of Diagnostic and Biomedical Sciences, School of Dentistry, The 
      University of Texas Health Science Center at Houston, 7500 Cambridge Street Room 
      4401, Houston, TX 77054, USA.
FAU - Grindel, Brian J
AU  - Grindel BJ
AD  - Department of Diagnostic and Biomedical Sciences, School of Dentistry, The 
      University of Texas Health Science Center at Houston, 7500 Cambridge Street Room 
      4401, Houston, TX 77054, USA.
AD  - Department of BioSciences, Weiss School of Natural Sciences, Rice University, 
      Houston, TX 77005, USA.
FAU - Farach-Carson, Mary C
AU  - Farach-Carson MC
AUID- ORCID: 0000-0002-4526-3088
AD  - Department of Diagnostic and Biomedical Sciences, School of Dentistry, The 
      University of Texas Health Science Center at Houston, 7500 Cambridge Street Room 
      4401, Houston, TX 77054, USA.
AD  - Department of BioSciences, Weiss School of Natural Sciences, Rice University, 
      Houston, TX 77005, USA.
AD  - Center for Theoretical Biological Physics, Rice University, Houston, TX 77005, 
      USA.
LA  - eng
GR  - P01CA0989-12/CA/NCI NIH HHS/United States
GR  - RP160015/Cancer Prevention and Research Institute of Texas/
GR  - RP170593/Cancer Prevention and Research Institute of Texas/
PT  - Journal Article
DEP - 20210322
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (persephin)
RN  - 0 (plexin)
RN  - 144713-63-3 (Neuropilin-1)
RN  - EC 3.4.24.23 (MMP7 protein, human)
RN  - EC 3.4.24.23 (Matrix Metalloproteinase 7)
SB  - IM
MH  - Cell Adhesion
MH  - Cell Adhesion Molecules/metabolism
MH  - Cell Line, Tumor
MH  - Cell Movement
MH  - Fluorescent Antibody Technique
MH  - Humans
MH  - Male
MH  - Matrix Metalloproteinase 7/*metabolism
MH  - Models, Biological
MH  - Nerve Tissue Proteins/*metabolism
MH  - Neuropilin-1/metabolism
MH  - Prostatic Neoplasms/etiology/*metabolism
MH  - Protein Binding
MH  - Proteolysis
PMC - PMC8004947
OTO - NOTNLM
OT  - dyscohesion
OT  - matrilysin/MMP-7
OT  - microtumors
OT  - migration
OT  - perlecan/HSPG2
OT  - prostate cancer
COIS- The authors declare no conflict of interest.
EDAT- 2021/04/04 06:00
MHDA- 2021/05/01 06:00
PMCR- 2021/03/22
CRDT- 2021/04/03 01:34
PHST- 2021/02/05 00:00 [received]
PHST- 2021/03/15 00:00 [revised]
PHST- 2021/03/15 00:00 [accepted]
PHST- 2021/04/03 01:34 [entrez]
PHST- 2021/04/04 06:00 [pubmed]
PHST- 2021/05/01 06:00 [medline]
PHST- 2021/03/22 00:00 [pmc-release]
AID - ijms22063218 [pii]
AID - ijms-22-03218 [pii]
AID - 10.3390/ijms22063218 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 Mar 22;22(6):3218. doi: 10.3390/ijms22063218.