Human α-Defensins HNPs-1, -2, and -3 in Renal Cell Carcinoma

Abstract

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.

Antimicrobial protein hCAP18/LL‐37 is highly expressed in breast cancer and is a putative growth factor for epithelial cells

“…In addition, synthetic biologically active LL-37 peptide significantly increased proliferation of HaCaT cells. These findings clearly contrast with the suggested antitumor effect proposed for antimicrobial peptides, but are consistent with recent findings by Müller et al 27 that human ␣-defensins may modulate progression of renal cell carcinoma (RCC). These defensins were found in tumor cells of RCC as well as in normal tubular epithelial of the kidney and at physiologic concentration-stimulated tumor cell proliferation.…”

“…This may reflect a complex yet strictly controlled regulation of hCAP18, as has been suggested for human ␣-defensins in renal cell carcinoma. 27 In our study, the highest hCAP18/LL-37 levels were detected among tumors with the highest histologic grade. Although the difference in hCAP18 expression between high-grade tumors on the one hand and low-grade and normal breast tissues is statistically significant, there is no strict correlation.…”

Identification of macrophage migration inhibitory factor and human neutrophil peptides 1–3 as potential biomarkers for gastric cancer

“…Human neutrophil peptides 1 -3 have been shown to be elevated in either tumour tissue or serum from patients with a range of cancer types (Müller et al, 2002;Lundy et al, 2004;Albrethsen et al, 2005;Melle et al, 2005), and we now extend this observation to gastric cancer. Human neutrophil peptides 1 -3 are also elevated by inflammation, for example, inflammatory bowel disease (Cunliffe et al, 2002) and so may lack specificity as tumour Figure 3 Partial least squares regression analysis using all peaks from CM10 and IMAC SELDI serum profiles of 50 gastric cancer patients (filled symbols) and 29 non-cancer controls (hollow symbols).…”

Proteomic analysis reveals successive aberrations in protein expression from healthy mucosa to invasive head and neck cancer

“…It is believed that they play an important role in the mucosal innate immune defense against a number of infectious diseases (reviewed in Ganz (2003)), and they are regarded as general markers for inflammation-related diseases, which includes epithelial cancers. Accordingly, overexpression of a-defensins in epithelial cancers is not a novel observation (Vlahou et al, 2001;Muller et al, 2002;Albrethsen et al, 2005). In HNSCC, increased expression of a-defensins 1-3 has been described in neutrophils that infiltrate HNSCCs (Lundy et al, 2004).…”