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.