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Protein bound polysaccharide PSK abrogates more efficiently experimental metastases derived from H-2 negative than
I Algarra1, A Collado, F Garrido
1Departamento de Analisis Clinicos e Immunologia, Hospital Universitario Virgen de las Nieves, Universidad de Granada, Spain.
Abstract:
We studied the effect of protein-bound polysaccharide PSK on metastatic colonization of BALB/c mice after intravenous injections of different syngeneic murine H-2 positive and H-2 negative tumor clones. The tumor lines used were different clones from chemically induced fibrosarcomas (GR9.B9, an H-2 negative clone from GR9 tumor, and B7.1.B4, an H-2 positive clone from B7.1 tumor). These clones were selected because of their different sensitivity to NK cytotoxicity, which was related to MHC class I expression. Pretreatment of mice with PSK inhibited metastatic colonization derived from B9 H-2 negative tumor cells. In contrast, lung colonization of PSK treated mice injected with B7.1.B4 H-2 positive tumor cells was higher, and differences in the number of colonies between untreated and PSK treated mice were small. In several experiments the effect of PSK was attenuated to a greater degree when high numbers of cells were injected. Abrogation of NK cells with anti-asialo GM1 serum significantly increased (in all tumors and at different cell doses) the number of metastatic colonies in comparison with untreated mice injected with tumors, regardless of the cell dose used. These results clearly suggest that NK cell activation in vivo by the protein bound polysaccharide PSK abrogates metastasis formation in mice. Abrogation was dependent on the H-2 phenotype even when pretreatment consisted of a single dose of PSK. This effect, related to the NK sensitivity of the tumor target, can be used to predict the effect of PSK in vivo.
Insights
Protein-bound polysaccharide PSK inhibits metastasis in mice by activating natural killer (NK) cells. This effect depends on the tumor
Area of Science:
- Immunology
- Oncology
- Pharmacology
Background:
- Metastasis remains a significant challenge in cancer treatment.
- Natural killer (NK) cells play a crucial role in immune surveillance against tumors.
- Protein-bound polysaccharide PSK is known for its immunomodulatory properties.
Purpose of the Study:
- To investigate the effect of PSK on metastatic colonization in mice.
- To determine the role of NK cells and tumor MHC class I expression in PSK's anti-metastatic activity.
Main Methods:
- BALB/c mice were injected intravenously with syngeneic murine H-2 positive and H-2 negative tumor clones.
- Mice were pretreated with PSK.
- NK cells were abrogated using anti-asialo GM1 serum.
- Metastatic colonization in the lungs was quantified.
Main Results:
- PSK inhibited metastasis of H-2 negative tumor cells but increased lung colonization of H-2 positive tumor cells.
- The anti-metastatic effect of PSK was dependent on NK cell activity and tumor's H-2 phenotype.
- Abrogation of NK cells significantly increased metastatic colonies for all tumor types.
Conclusions:
- PSK activates NK cells in vivo, leading to abrogation of metastasis.
- The efficacy of PSK in preventing metastasis is influenced by the tumor's H-2 phenotype and NK cell sensitivity.
- This study highlights the potential of PSK as an immunotherapeutic agent for cancer metastasis.