Protein-bound polysaccharide PSK inhibits tumor invasiveness by down-regulation of TGF-beta1 and MMPs.
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.
Zhang
H
H
Department of Hospital Clinical Laboratory, Saga Medical School, Japan.
Morisaki
T
T
Matsunaga
H
H
Sato
N
N
Uchiyama
A
A
Hashizume
K
K
Nagumo
F
F
Tadano
J
J
Katano
M
M
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003094:Collagen; D015536:Down-Regulation; D004338:Drug Combinations; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007797:Laminin; D020782:Matrix Metalloproteinases / Q000187:drug effects* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000187:drug effects* / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000473:pathology; D011509:Proteoglycans / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000187:drug effects* / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology
D000276:Adjuvants, Immunologic; D000903:Antibiotics, Antineoplastic; D004338:Drug Combinations; D007797:Laminin; D009363:Neoplasm Proteins; D011509:Proteoglycans; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C059485:matrigel; C010770:polysaccharide-K; D003094:Collagen; D020782:Matrix Metalloproteinases