Role of natural killer cells and macrophages in the nonspecific resistance to tumors in mice stimulated with SMANCS, a polymer-conjugated derivative of neocarzinostatin

Fujio Suzuki, Richard B. Pollard, Satomi Uchimura, Tetsuo Munakata, Hiroshi Maeda

Research output: Contribution to journalArticle

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Abstract

Copoly(styrene-maleic acid)-conjugated neocarzinostatin (SMANCS), a lipophilic derivative of the proteinaceous antitumor antibiotic neocarzinostatin, has been reported to stimulate a nonspecific resistance to tumors (NSRT) in solid tumor-bearing mice, in addition to its chemotherapeutic antitumor effect through the arrest of DNA synthesis by direct DNA strand scission. In the present study, splenic or peritoneal effector cells were used to investigate the ability of SMANCS to augment natural killer (NK) cell activity and to generate cytostatic macrophages (A-Mφ). Splenic NK cell activity augmented by SMANCS was characterized by cytotoxicity to various target cells, nylon wool nonadherence, and sensitivity to treatment with anti-asialo-GM1 antiserum or monoclonal anti-Thy-1.2 antibody followed by complement. The A-Mφ generated by SMANCS stimulation were characterized by their adherence to a plastic surface coated with fetal calf serum and their ability to phagocytize carbonyl-iron. The maximum level of NK cell activity in the spleens of mice was detected 3 days after i.v. injection of SMANCS, and the highest activity of the peritoneal A-Mφ was demonstrated in mice 4 days after SMANCS treatment. On the other hand, the NSRT of mice stimulated with SMANCS was not detectable in mice treated with carrageenan or trypwi blue, whereas SMANCS-stimulated NSRT was observed in mice treated with anti-asialo-GM1 antiserum. The NSRT that was stimulated with SMANCS was also demonstrated in mice homozygous for the beige mutation and their non-beige littermates, when NK cell-resistant EL-4 thymoma was used as a tumor target. These results suggest that the expression of NSRT of mice stimulated with SMANCS may require the function of A-Mφ, although NK cell activity was also augmented in spleens of mice by administration of SMANCS.

Original languageEnglish (US)
Pages (from-to)3897-3904
Number of pages8
JournalCancer Research
Volume50
Issue number13
StatePublished - Jul 1 1990

Fingerprint

Zinostatin
Styrene
Natural Killer Cells
Polymers
Macrophages
Neoplasms
Immune Sera
maleic acid
Spleen
Thymoma
Wool
Carrageenan
DNA
Nylons
Cytostatic Agents
Plastics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Role of natural killer cells and macrophages in the nonspecific resistance to tumors in mice stimulated with SMANCS, a polymer-conjugated derivative of neocarzinostatin. / Suzuki, Fujio; Pollard, Richard B.; Uchimura, Satomi; Munakata, Tetsuo; Maeda, Hiroshi.

In: Cancer Research, Vol. 50, No. 13, 01.07.1990, p. 3897-3904.

Research output: Contribution to journalArticle

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abstract = "Copoly(styrene-maleic acid)-conjugated neocarzinostatin (SMANCS), a lipophilic derivative of the proteinaceous antitumor antibiotic neocarzinostatin, has been reported to stimulate a nonspecific resistance to tumors (NSRT) in solid tumor-bearing mice, in addition to its chemotherapeutic antitumor effect through the arrest of DNA synthesis by direct DNA strand scission. In the present study, splenic or peritoneal effector cells were used to investigate the ability of SMANCS to augment natural killer (NK) cell activity and to generate cytostatic macrophages (A-Mφ). Splenic NK cell activity augmented by SMANCS was characterized by cytotoxicity to various target cells, nylon wool nonadherence, and sensitivity to treatment with anti-asialo-GM1 antiserum or monoclonal anti-Thy-1.2 antibody followed by complement. The A-Mφ generated by SMANCS stimulation were characterized by their adherence to a plastic surface coated with fetal calf serum and their ability to phagocytize carbonyl-iron. The maximum level of NK cell activity in the spleens of mice was detected 3 days after i.v. injection of SMANCS, and the highest activity of the peritoneal A-Mφ was demonstrated in mice 4 days after SMANCS treatment. On the other hand, the NSRT of mice stimulated with SMANCS was not detectable in mice treated with carrageenan or trypwi blue, whereas SMANCS-stimulated NSRT was observed in mice treated with anti-asialo-GM1 antiserum. The NSRT that was stimulated with SMANCS was also demonstrated in mice homozygous for the beige mutation and their non-beige littermates, when NK cell-resistant EL-4 thymoma was used as a tumor target. These results suggest that the expression of NSRT of mice stimulated with SMANCS may require the function of A-Mφ, although NK cell activity was also augmented in spleens of mice by administration of SMANCS.",
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