The role of neutrophils as cytotoxic cells in lung metastasis: suppression of tumor cell metastasis by a biological response modifier (PSK).

We aimed to determine the role of neutrophils and the usefulness of a protein-bound polysaccharide (PSK) in the suppression of tumor cell metastasis in the lung in vivo. Circulating neutrophils collected frm tumor-bearing animals (Line-10 hepatocarcinoma) induced a marked decrease in the size and number of metastatic foci in the lung. Although pulmonary macrophages (PAMs), lymphocyte and eosinophil in bronchoalveolar lavage (BAL) fluid increased following tumor cell inoculation, in addition to these findings we found that PSK caused an increase in BAL neutrophil levels causing increased of target cell toxicity and a marked decrease in the size and the number of lung metastatic foci. Superoxide anion generation of blood neutrophils collected from PSK-treated animals with metastasis showed forward acceleration. The presence of neutrophil chemotactic factors was confirmed in the BAL fluid of PSK-treated animals with metastasis, but not leukotriene B4. The results suggest that modulation of the tumor cell microenvironment by activation of neutrophils may prove to be an additional modality in treatment strategy by combining PSK as a biological response modifier with conventional therapies for lung metastasis.