PMID- 30347648
OWN - NLM
STAT- MEDLINE
DCOM- 20190114
LR  - 20190114
IS  - 1420-3049 (Electronic)
IS  - 1420-3049 (Linking)
VI  - 23
IP  - 10
DP  - 2018 Oct 19
TI  - Unfractionated and Low Molecular Weight Heparin Reduce Platelet Induced 
      Epithelial-Mesenchymal Transition in Pancreatic and Prostate Cancer Cells.
LID - 10.3390/molecules23102690 [doi]
LID - 2690
AB  - The interaction with platelets is of crucial importance for tumor cells passing 
      through hematogenous metastasis. Platelets protect cancer cells from immune 
      surveillance and exhibit many other prometastatic effects. Notably, platelets can 
      change the epithelial tumor phenotype, a process termed epithelial-mesenchymal 
      transition (EMT), which confers stem cell-like properties onto tumor cells 
      associated with an increased motility and drug resistance. The aim of the study 
      is to investigate the impact of heparin on the platelet induced EMT program in 
      pancreatic and prostate tumor cells. Platelet activation and interaction with 
      cancer cells were determined by static adhesion assays. Applying ELISAs, the 
      platelet release of EMT inducing mediators was quantified. EMT marker protein 
      expression by tumor cells was explored by western blot and qPCR. Our data show 
      that different tumor cell entities have different platelet binding capacities and 
      also that a weak interaction is sufficient to change tumor cell phenotype. 
      Additionally, unfractionated heparin (UFH) as well as low molecular weight 
      heparin (LMWH) reduced tumor cell platelet interaction. Subsequently, attenuated 
      platelet-derived mediator release resulted in reduced EMT marker protein and 
      transcription factor expression by the cancer cells and decreased cell migration. 
      These data suggest that heparin reduces platelet induced EMT program and prevents 
      the formation of cancer cells with stem cell-like properties. This additional 
      mechanism argues for the use of heparin in oncological applications.
FAU - Ponert, Jan Moritz
AU  - Ponert JM
AD  - Department of Pharmacy, University of Bonn, An der Immenburg 4, 53121 Bonn, 
      Germany. moritz.ponert@uni-bonn.de.
FAU - Gockel, Lukas Maria
AU  - Gockel LM
AD  - Department of Pharmacy, University of Bonn, An der Immenburg 4, 53121 Bonn, 
      Germany. Lukas.Gockel@uni-bonn.de.
FAU - Henze, Svenja
AU  - Henze S
AD  - Department of Pharmacy, University of Bonn, An der Immenburg 4, 53121 Bonn, 
      Germany. svenja.henze@uni-bonn.de.
FAU - Schlesinger, Martin
AU  - Schlesinger M
AD  - Department of Pharmacy, University of Bonn, An der Immenburg 4, 53121 Bonn, 
      Germany. martin.schlesinger@uni-bonn.de.
LA  - eng
PT  - Journal Article
DEP - 20181019
PL  - Switzerland
TA  - Molecules
JT  - Molecules (Basel, Switzerland)
JID - 100964009
RN  - 0 (Heparin, Low-Molecular-Weight)
SB  - IM
MH  - Blood Platelets/*drug effects/metabolism
MH  - Cell Adhesion/drug effects
MH  - Cell Line, Tumor
MH  - Cell Movement/drug effects/genetics
MH  - Epithelial-Mesenchymal Transition/drug effects/genetics
MH  - Heparin, Low-Molecular-Weight/*pharmacology
MH  - Humans
MH  - Male
MH  - Pancreatic Neoplasms/blood/*drug therapy/pathology
MH  - Platelet Activation/drug effects
MH  - Prostatic Neoplasms/blood/*drug therapy/genetics/pathology
PMC - PMC6222876
OTO - NOTNLM
OT  - EMT
OT  - cancer stem cells
OT  - enoxaparin
OT  - epithelial-mesenchymal transition
OT  - heparin
OT  - platelet
OT  - tumor
COIS- The authors declare no conflict of interest.
EDAT- 2018/10/24 06:00
MHDA- 2019/01/15 06:00
PMCR- 2018/10/19
CRDT- 2018/10/24 06:00
PHST- 2018/09/28 00:00 [received]
PHST- 2018/10/12 00:00 [revised]
PHST- 2018/10/18 00:00 [accepted]
PHST- 2018/10/24 06:00 [entrez]
PHST- 2018/10/24 06:00 [pubmed]
PHST- 2019/01/15 06:00 [medline]
PHST- 2018/10/19 00:00 [pmc-release]
AID - molecules23102690 [pii]
AID - molecules-23-02690 [pii]
AID - 10.3390/molecules23102690 [doi]
PST - epublish
SO  - Molecules. 2018 Oct 19;23(10):2690. doi: 10.3390/molecules23102690.