Human alpha-defensins HNPs-1, -2, and -3 in renal cell carcinoma: influences on tumor cell proliferation.
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.
Müller
Claudia A
CA
Department II, Section of TransplantationImmunology and Immunohematology, Medical University Clinic, Eberhard-Karls-University, Tübingen, Germany. claudia.mueller@uni-tuebingen.de
Markovic-Lipkovski
Jasmina
J
Klatt
Tatjana
T
Gamper
Jutta
J
Schwarz
Gerold
G
Beck
Hermann
H
Deeg
Martin
M
Kalbacher
Hubert
H
Widmann
Susanne
S
Wessels
Johannes T
JT
Becker
Volker
V
Müller
Gerhard A
GA
Flad
Thomas
T
D017951:Antigen Presentation / Q000502:physiology; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000502:physiology; D002469:Cell Separation; D005434:Flow Cytometry; D006801:Humans; D007680:Kidney Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D012016:Reference Values; D014407:Tumor Cells, Cultured; D023084:alpha-Defensins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
D012333:RNA, Messenger; D023084:alpha-Defensins; C406413:human neutrophil peptide 1; C406416:human neutrophil peptide 2; C406427:human neutrophil peptide 3