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Effects of the immunomodulator PSK on growth of human prostate adenocarcinoma in immunodeficient mice
D D Mickey1, P S Bencuya, K Foulkes
1Department of Surgery, University of North Carolina, Chapel Hill.
Abstract:
Tumor growth alterations were studied using an immunomodulator, PSK. Four human prostate tumor lines were grown in two types of immunodeficient mice. Two of the lines were selected because they are able to metastasize to lungs in host animals. Outbred NIH Swiss athymic mice having normal natural killer cells and athymic Beige mice deficient in natural killer cells were used as animal hosts. PSK treatment was given to tumor-bearing hosts to some animals soon after solid tumors were injected and to others after solid tumors were well-established. Low dose cyclophosphamide was given to some animals to decrease host natural killer cells and polyinosinic-polycytidylic acid (poly I:C) was given to other animals to increase natural killer cell activity. Measurement of tumor doubling times, host survival and metastatic capabilities showed that either poly I:C or PSK treatment in NIH Swiss animals soon after tumor cells were injected significantly increased tumor doubling times and host survival and decreased the incidence and number of metastatic lung lesions. Two of the tumor lines incapable of metastasizing in NIH Swiss mice were metastatic in the Beige athymic, natural killer-cell-deficient animals.
Insights
The immunomodulator PSK and poly I:C enhanced immune response in mice, significantly increasing tumor doubling times and host survival while reducing lung metastasis in prostate cancer models.
Area of Science:
- Immunology and Cancer Research
- Pharmacology of Immunomodulators
Background:
- Prostate tumor growth and metastasis are complex processes influenced by the host immune system.
- Natural killer (NK) cells play a crucial role in immune surveillance against tumors.
- Immunomodulators like PSK and poly I:C can modulate immune responses.
Purpose of the Study:
- To investigate the effects of the immunomodulator PSK on tumor growth and metastasis in prostate cancer models.
- To evaluate the role of natural killer (NK) cells in mediating the anti-tumor effects of PSK and poly I:C.
- To assess the impact of NK cell activity on tumor progression and metastatic potential.
Main Methods:
- Four human prostate tumor lines were xenografted into two types of immunodeficient mice: NIH Swiss (normal NK cells) and athymic Beige (deficient NK cells).
- Mice were treated with PSK, polyinosinic-polycytidylic acid (poly I:C) to enhance NK activity, or cyclophosphamide to deplete NK cells.
- Tumor growth (doubling time), host survival, and metastatic burden (lung lesions) were measured.
Main Results:
- PSK or poly I:C treatment in NIH Swiss mice significantly increased tumor doubling times and host survival.
- These treatments also decreased the incidence and number of lung metastatic lesions in NIH Swiss mice.
- Tumor lines that did not metastasize in NK-competent NIH Swiss mice showed metastatic potential in NK-deficient athymic Beige mice.
Conclusions:
- PSK and poly I:C demonstrate significant anti-tumor and anti-metastatic effects in immunocompetent mouse models.
- Natural killer (NK) cell activity is critical for controlling prostate tumor growth and preventing lung metastasis.
- The findings highlight the therapeutic potential of immunomodulators targeting NK cell function in prostate cancer.