PMID- 27572115
OWN - NLM
STAT- MEDLINE
DCOM- 20170310
LR  - 20181113
IS  - 1791-2431 (Electronic)
IS  - 1021-335X (Print)
IS  - 1021-335X (Linking)
VI  - 36
IP  - 5
DP  - 2016 Nov
TI  - Heparin regulates B6FS cell motility through a FAK/actin cytoskeleton axis.
PG  - 2471-2480
LID - 10.3892/or.2016.5057 [doi]
AB  - Soft tissue sarcomas are rare, heterogeneous tumors of mesenchymal origin with an 
      aggressive behavior. Heparin is a mixture of heavily sulfated, linear 
      glycosaminoglycan (GAG) chains, which participate in the regulation of various 
      cell biological functions. Heparin is considered to have significant anticancer 
      capabilities, although the mechanisms involved have not been fully defined. In 
      the present study, the effects of unfractionated heparin (UFH) and 
      low‑molecular‑weight heparin (LMWH) on B6FS fibrosarcoma cell motility were 
      examined. Both preparations of heparin were shown to both enhance B6FS cell 
      adhesion (p<0.01 and p<0.05), and migration (p<0.05), the maximal effect being 
      evident at the concentration of 10 microg/ml. The utilization of FAK‑deficient cells 
      demonstrated that the participation of FAK was obligatory for heparin‑dependent 
      fibrosarcoma cell adhesion (p<0.05). The results of confocal microscopy indicated 
      that heparin was taken up by the B6FS cells, and that UFH and LMWH induced 
      F‑actin polymerization. Heparitinase digestion demonstrated that the endogenous 
      heparan sulfate (HS) chains did not affect the motility of the B6FS 
      cells (p>0.05, not significant). In conclusion, both UFH and LMWH, through a 
      FAK/actin cytoskeleton axis, promoted the adhesion and migration of B6FS 
      fibrosarcoma cells. Thus, our findings indicate that the responsiveness of 
      fibrosarcoma cells to the exogenous heparin/HS content of the cancer 
      microenvironment may play a role in their ability to become mobile and 
      metastasize.
FAU - Voudouri, Kallirroi
AU  - Voudouri K
AD  - Laboratory of Anatomy‑Histology‑Embryology, School of Medicine, University of 
      Crete, Heraklion 71003, Greece.
FAU - Nikitovic, Dragana
AU  - Nikitovic D
AD  - Laboratory of Anatomy‑Histology‑Embryology, School of Medicine, University of 
      Crete, Heraklion 71003, Greece.
FAU - Berdiaki, Aikaterini
AU  - Berdiaki A
AD  - Laboratory of Anatomy‑Histology‑Embryology, School of Medicine, University of 
      Crete, Heraklion 71003, Greece.
FAU - Papachristou, Dionysios J
AU  - Papachristou DJ
AD  - Laboratory of Anatomy‑Histology‑Embryology, School of Medicine, University of 
      Patras, Patras 23001, Greece.
FAU - Tsiaoussis, John
AU  - Tsiaoussis J
AD  - Laboratory of Anatomy‑Histology‑Embryology, School of Medicine, University of 
      Crete, Heraklion 71003, Greece.
FAU - Spandidos, Demetrios A
AU  - Spandidos DA
AD  - Laboratory of Virology, School of Medicine, University of Crete, Heraklion 71003, 
      Greece.
FAU - Tsatsakis, Aristides M
AU  - Tsatsakis AM
AD  - Laboratory of Toxicology, School of Medicine, University of Crete, 
      Heraklion 71003, Greece.
FAU - Tzanakakis, George N
AU  - Tzanakakis GN
AD  - Laboratory of Anatomy‑Histology‑Embryology, School of Medicine, University of 
      Crete, Heraklion 71003, Greece.
LA  - eng
PT  - Journal Article
DEP - 20160830
PL  - Greece
TA  - Oncol Rep
JT  - Oncology reports
JID - 9422756
RN  - 0 (Anticoagulants)
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - 9005-49-6 (Heparin)
RN  - EC 2.7.10.2 (Focal Adhesion Kinase 1)
RN  - EC 2.7.10.2 (PTK2 protein, human)
SB  - IM
MH  - Actin Cytoskeleton/genetics/metabolism
MH  - Anticoagulants/*administration & dosage
MH  - Cell Adhesion/drug effects
MH  - Cell Line, Tumor
MH  - Cell Movement/drug effects
MH  - Fibrosarcoma/*drug therapy/genetics/pathology
MH  - Focal Adhesion Kinase 1/*genetics/metabolism
MH  - Heparin/administration & dosage
MH  - Heparin, Low-Molecular-Weight/administration & dosage
MH  - Humans
MH  - Sarcoma/*drug therapy/genetics/pathology
PMC - PMC5055209
EDAT- 2016/10/26 06:00
MHDA- 2017/03/11 06:00
PMCR- 2016/08/30
CRDT- 2016/08/31 06:00
PHST- 2016/05/04 00:00 [received]
PHST- 2016/08/11 00:00 [accepted]
PHST- 2016/10/26 06:00 [pubmed]
PHST- 2017/03/11 06:00 [medline]
PHST- 2016/08/31 06:00 [entrez]
PHST- 2016/08/30 00:00 [pmc-release]
AID - or-36-05-2471 [pii]
AID - 10.3892/or.2016.5057 [doi]
PST - ppublish
SO  - Oncol Rep. 2016 Nov;36(5):2471-2480. doi: 10.3892/or.2016.5057. Epub 2016 Aug 30.