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(American Journal of Pathology. 2002;160:1311-1324.)
© 2002 American Society for Investigative Pathology

Regular Articles

Human {alpha}-Defensins HNPs-1, -2, and -3 in Renal Cell Carcinoma

Influences on Tumor Cell Proliferation

Claudia A. Müller*, Jasmina Markovic-Lipkovski{dagger}, Tatjana Klatt*, Jutta Gamper*, Gerold Schwarz{ddagger}, Hermann Beck§, Martin Deeg*, Hubert Kalbacher{ddagger}, Susanne Widmann*, Johannes T. Wessels, Volker Becker§, Gerhard A. Müller§ and Thomas Flad*

From Department II,* Section of TransplantationImmunology and Immunohematology, Medical University Clinic, and theMedical and Natural Sciences Research Center,{ddagger}and the Children’s Hospital, Eberhard-Karls-University, Tübingen, Germany; the Department ofNephrology and Rheumatology,§ Center ofInternal Medicine, Georg-August-University, Göttingen, Germany;and the Medical Faculty,{dagger} Institute ofPathology, University of Belgrade, Belgrade, Yugoslavia

The {alpha}-defensins human neutrophil peptides (HNPs)-1, -2, and -3 have been described as cytotoxic peptides with restricted expression in neutrophils and in some lymphocytes. In this study we report that HNPs-1, -2, and -3 are also expressed in renal cell carcinomas (RCCs). Several RCC lines were found to express mRNA as well as the specific peptides of HNP-1, -2, and -3 demonstrated by reverse transcriptase-polymerase chain reaction, mass spectrometric, and flow cytometric analyses. At physiological concentrations HNPs-1, -2, and -3 stimulated cell proliferation of selected RCC lines in vitro but at high concentrations were cytotoxic for all RCC lines tested. As in RCC lines, {alpha}-defensins were also detected in vivo in malignant epithelial cells of 31 RCC tissues in addition to their expected presence in neutrophils. In most RCC cases randomly, patchy immunostaining of {alpha}-defensins on epithelial cells surrounding neutrophils was seen, but in six tumors of higher grade malignancy all tumor cells were diffusely stained. Cellular necrosis observed in RCC tissues in association with extensive patches of HNP-1, -2, and -3, seemed to be related to high concentrations of {alpha}-defensins. The in vitro and in vivo findings suggest that {alpha}-defensins are frequent peptide constituents of malignant epithelial cells in RCC with a possible direct influence on tumor proliferation.




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