Etiology and Pathogenesis > Invasion | Integrative Medicine > PSK and other Polysaccharides  

Abstract

Protein-bound polysaccharide PSK inhibits tumor invasiveness by down-regulation of TGF-beta1 and MMPs

Zhang H, Morisaki T, Matsunaga H, Sato N, Uchiyama A, Hashizume K, Nagumo F, Tadano J, Katano M

Department of Hospital Clinical Laboratory, Saga Medical School, Japan

Transforming growth factor beta1 (TGF-beta1) and matrix metalloproteinases (MMPs) produced by tumor cells play important roles in tumor invasion.
PSK, a protein-bound polysaccharide, is widely used in Japan as an immunopotentiating biological response modifier for cancer patients.
In this study, we focused on the effects of PSK on invasiveness, TGF-beta1 production, and MMPs expression in two human tumor cell lines, pancreatic cancer cell line (NOR-P1) and gastric cancer cell line (MK-1P3).
PSK significantly decreased the invasiveness of both cell lines through Matrigel-coated filters but did not affect cell viability, proliferation, or adhesion.
Decreased invasion was associated with the inhibition of TGF-beta1, MMP-2, and MMP-9 at both mRNA and protein levels as assessed by reverse transcriptase-polymerase chain reaction, gelatin zymography, and enzyme-linked immunosorbent assay.
Antibody against TGF-beta1 neutralized the MMP activities of both cell lines.
PSK also suppressed the expression of urokinase plasminogen activator (uPA) and uPA receptor but did not change plasminogen activator inhibitor-1 (PAI-1) expression.
Western blot analysis showed that PSK reduced uPA protein expression but not PAI-1 expression in the both cell lines.
These results indicate that PSK suppresses tumor cell invasiveness through down-regulation of several invasion-related factors including TGF-beta1, uPA, MMP-2, and MMP-9.

PMID: 11448066 [PubMed - indexed for MEDLINE]