Orally Administered Rhamnan Sulfate from Monostroma nitidum Significantly Inhibits Melanoma Metastasis in Lungs and Aorta of Mice Implanted with B16 Cells

Tumor metastasis is closely associated with coagulation and inflammation, particularly via thrombin–PAR1 signaling. However, the potential of natural polysaccharides such as rhamnan sulfate (RS) to modulate these pathways and suppress metastasis remains unclear. We aimed to investigate the effects of orally administered RS derived from Monostroma nitidum on melanoma metastasis and its underlying mechanisms. Male C57BL/6J mice were orally administered water or RS daily. On day 8, saline or B16 melanoma cells were injected intravenously. Mice were treated for 21 days and divided into four groups (control, RS-only, M + W, and M + RS; n = 5/group). Metastasis and related molecular factors were analyzed in plasma, lung, and aortic tissues. Significant lung and aortic metastases were observed in the M + W group but were markedly suppressed in the M + RS group. RS reduced the expression of inflammatory factors (e.g., IL-6, PAR1), proteases, leukocyte activation markers, complement factors, angiogenic factors, and EMT-related factors. Conversely, thrombin, thrombomodulin, plasmin, TAFIa, and tight junction proteins were increased in RS-treated mice. RS suppresses melanoma metastasis by modulating thrombin–PAR1-mediated inflammation and associated pathways. These findings suggest RS as a potential therapeutic agent, although further mechanistic and clinical studies are required.