title: Heparin regulates B6FS cell motility through a FAK/actin cytoskeleton axis.
abstract: 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 µg/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.
authors: Laboratory of Anatomy‑Histology‑Embryology, School of Medicine, University of Crete, Heraklion 71003, Greece.
authors: Kallirroi
authors: K
authors: Voudouri
authors: Laboratory of Anatomy‑Histology‑Embryology, School of Medicine, University of Crete, Heraklion 71003, Greece.
authors: Dragana
authors: D
authors: Nikitovic
authors: Laboratory of Anatomy‑Histology‑Embryology, School of Medicine, University of Crete, Heraklion 71003, Greece.
authors: Aikaterini
authors: A
authors: Berdiaki
authors: Laboratory of Anatomy‑Histology‑Embryology, School of Medicine, University of Patras, Patras 23001, Greece.
authors: Dionysios J
authors: DJ
authors: Papachristou
authors: Laboratory of Anatomy‑Histology‑Embryology, School of Medicine, University of Crete, Heraklion 71003, Greece.
authors: John
authors: J
authors: Tsiaoussis
authors: Laboratory of Virology, School of Medicine, University of Crete, Heraklion 71003, Greece.
authors: Demetrios A
authors: DA
authors: Spandidos
authors: Laboratory of Toxicology, School of Medicine, University of Crete, Heraklion 71003, Greece.
authors: Aristides M
authors: AM
authors: Tsatsakis
authors: Laboratory of Anatomy‑Histology‑Embryology, School of Medicine, University of Crete, Heraklion 71003, Greece.
authors: George N
authors: GN
authors: Tzanakakis
mesh_terms: D008841:Actin Cytoskeleton / Q000235:genetics / Q000378:metabolism; D000925:Anticoagulants / Q000008:administration & dosage*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D005354:Fibrosarcoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D051417:Focal Adhesion Kinase 1 / Q000235:genetics* / Q000378:metabolism; D006493:Heparin / Q000008:administration & dosage; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage; D006801:Humans; D012509:Sarcoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
chemical_list: D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D006493:Heparin; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human