Inhibitors of monocyte responses to chemotaxins are present in human cancerous effusions and react with monoclonal antibodies to the P15(E) structural protein of retroviruses.

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Abstract

Individuals with cancer have previously been shown to have abnormal chemotactic responsiveness. Surgical removal of the tumor often resulted in normalization of monocyte function, which suggests that human neoplasms might inhibit monocyte chemotaxis by release of soluble mediators. We therefore examined the effects of cancerous effusions on monocyte polarization, i.e., the rapid change in monocyte morphology from round to a triangular "motile" configuration in response to chemoattractants. All 17 malignant effusions, representing 15 tumor types, inhibited monocyte polarization induced by the chemoattractant N-formyl-methionyl-leucyl-phenylalanine by 45-89% (mean 55.9 +/- 12.7%, P less than 0.01) in blinded assays. None of 17 benign effusions signigicantly inhibited polarization (0-15%, mean 6.2 +/- 4.2%). Dilutions of cancerous effusions as low as 1:200 produced inhibition that was time, temperature, and dose dependent . Monocyte polarization induced by activated serum or by chemotactic lymphokine was also blocked by cancerous effusions. The inhibitory activity affected the monocyte directly, and did not destroy the chemoattractant or block the polarization of granulocytes to chemotactic factors. High pressure liquid chromatography of five cancerous fluids revealed three peaks of inhibitory activity: greater than or equal to 200,000, 46,000 +/- 13,000, and 21,000 +/- 3,000 daltons. Fractionation of noncancerous effusions revealed only small amounts of the highest molecular weight inhibitory activity. The inhibitory activity in cancerous effusion was heat stable (56 degrees C, 30 min), trypsin sensitive, and could be absorbed by three different monoclonal antibodies reactive to P15(E), a structural component of type C retroviruses. In contrast, six monoclonal antibodies with other specificities had no effect on the inhibitors of polarization. This study demonstrates that human cancerous effusions contain novel proteins that are potent inhibitors of monocyte function and that are recognized by antibodies reactive to the P15(E) component of retroviruses. By producing such factors, tumor cells may subvert monocyte-mediated surveillance.

Authors

G Cianciolo, J Hunter, J Silva, J S Haskill, R Snyderman