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This study investigated the effects of malignant and benign effusions on monocyte polarization, a key aspect of chemotactic responsiveness. Researchers found that all 17 cancerous effusions significantly inhibited monocyte polarization induced by various chemoattractants, whereas benign effusions did not exhibit this inhibitory activity. The inhibitory factors were identified as heat-stable, trypsin-sensitive proteins with specific molecular weights that reacted with monoclonal antibodies targeting the P15(E) structural protein of retroviruses. The paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.
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.
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Research Article Free access | 10.1172/JCI110338
Find articles by Cianciolo, G. in: PubMed | Google Scholar
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Published October 1, 1981 - More info
Published in
Volume 68, Issue 4
on
October 1, 1981
J Clin Invest. 1981;68(4):831–844. https://doi.org/10.1172/JCI110338.
© 1981 The American Society for Clinical Investigation
J Clin Invest. 1981;68(4):831–844. https://doi.org/10.1172/JCI110338.
© 1981 The American Society for Clinical Investigation
Published October 1, 1981
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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.
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Version history
- Version 1 (October 1, 1981): No description
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ISSN: 0021-9738 (print), 1558-8238 (online)
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