Aminated fucoidan promotes the invasion of 3 LL cells through reconstituted basement membrane: its possible mechanism of action.
Fucoidan is reported to have an antimetastatic activity. In the present study, we prepared an amino group-introduced derivative of fucoidan and examined its effect on the invasion of 3 LL cells through a reconstituted basement membrane (MatrigelTM). Unlike native fucoidan, the aminated derivative promoted the tumor cell invasion: maximal promotion (240% of control invasion) was obtained with 5 micrograms/ml. However, with higher concentrations (10-30 micrograms/ml) of the fucoidan derivative, the promotion was gradually reduced to 130% of control. Both native and aminated fucoidans inhibited specifically the attachment of 3 LL cells to laminin. Interestingly, aminated fucoidan, unlike the native one, promoted the tumor cell adhesion to immobilized synthetic laminin B 1 chain peptide, YIGSR, over a concentration range of 0.5-5 micrograms/ml. Higher concentrations (7-20 micrograms/ml) of the aminated derivative suppressed the adhesive ability of 3 LL cells to YIGSR. 3 LL cells secreted a 50-kDa form of urokinase-type plasminogen activator (u-PA) in the culture medium. Addition of aminated fucoidan (5 micrograms/ml) or YIGSR (10 micrograms/ml) resulted in a 1.7-fold increase in u-PA activity. This effect was enhanced up to 3.5-fold when both substances were simultaneously added. The addition of native fucoidan had no effect. The present results suggest that the 67-kDa receptor-mediated binding of 3 LL cells to laminin activates their invasiveness, especially by enhancing the extracellular u-PA levels. Aminated, but not native, fucoidan may act to enhance the laminin-receptor interaction at the limited concentration range.
Soeda
S
S
Department of Biochemistry, Faculty of Pharmaceutical Sciences, Fukuoka University, Japan.
Ishida
S
S
Honda
O
O
Shimeno
H
H
Nagamatsu
A
A
D000586:Amination; D000595:Amino Acid Sequence; D000818:Animals; D000925:Anticoagulants / Q000633:toxicity*; D001485:Basement Membrane / Q000187:drug effects / Q000502:physiology; D018827:Carcinoma, Lewis Lung / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure*; D003094:Collagen / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D011134:Polysaccharides / Q000378:metabolism / Q000633:toxicity*; D017474:Receptors, Laminin / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D000925:Anticoagulants; D005353:Fibronectins; D007797:Laminin; D011134:Polysaccharides; D017474:Receptors, Laminin; D003094:Collagen; C007789:fucoidan; D014568:Urokinase-Type Plasminogen Activator