Characteristics of patients with pancreatic cancer expressing a novel cancer cachectic factor

Wigmore, Stephen J.; Todorov, Penio; Barber, Matthew D.; Ross, James A.; Tisdale, Michael J.; Fearon, K.C.H.

doi:10.1046/j.1365-2168.2000.01317.x

Cited by 111 publications

(68 citation statements)

References 12 publications

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“…Posttranslational modifications of DCD produce peptides with different functions: survival‐promoting peptide and the antimicrobial DCD‐1 protein. In addition, tumor cells can generate another peptide called proteolysis‐inducing factor (PIF) that is associated with cachexia in cancer patients 47. Although it is known that melanoma cells express DCD,48, 49 until now this protein has not been associated with malignancy.…”

Section: Discussionmentioning

confidence: 99%

Vitronectin and dermcidin serum levels predict the metastatic progression of AJCC I–II early‐stage melanoma

Ortega-Martinez

Gardeazábal

Erramuzpe

et al. 2016

Intl Journal of Cancer

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Like many cancers, an early diagnosis of melanoma is fundamental to ensure a good prognosis, although an important proportion of stage I–II patients may still develop metastasis during follow‐up. The aim of this work was to discover serum biomarkers in patients diagnosed with primary melanoma that identify those at a high risk of developing metastasis during the follow‐up period. Proteomic and mass spectrophotometry analysis was performed on serum obtained from patients who developed metastasis during the first years after surgery for primary tumors and compared with that from patients who remained disease‐free for more than 10 years after surgery. Five proteins were selected for validation as prognostic factors in 348 melanoma patients and 100 controls by ELISA: serum amyloid A and clusterin; immune system proteins; the cell adhesion molecules plakoglobin and vitronectin and the antimicrobial protein dermcidin. Compared to healthy controls, melanoma patients have high serum levels of these proteins at the moment of melanoma diagnosis, although the specific values were not related to the histopathological stage of the tumors. However, an analysis based on classification together with multivariate statistics showed that tumor stage, vitronectin and dermcidin levels were associated with the metastatic progression of patients with early‐stage melanoma. Although melanoma patients have increased serum dermcidin levels, the REPTree classifier showed that levels of dermcidin <2.98 μg/ml predict metastasis in AJCC stage II patients. These data suggest that vitronectin and dermcidin are potent biomarkers of prognosis, which may help to improve the personalized medical care of melanoma patients and their survival.

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Section: Discussionmentioning

confidence: 99%

Vitronectin and dermcidin serum levels predict the metastatic progression of AJCC I–II early‐stage melanoma

Ortega-Martinez

Gardeazábal

Erramuzpe

et al. 2016

Intl Journal of Cancer

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“…Several in vitro studies of PIF have used immunological methods of detection and have always required cell lysates, as opposed to supernatants, for success (Todorov et al, 1996(Todorov et al, , 1999. In contrast with these findings, in vivo studies using the same antibody have demonstrated glycosylated PIF in urine and suggest that it may be found, bound to albumin, in serum, suggesting that the molecule may be secreted (Todorov et al, 1996;Wigmore et al, 2000). The DCD-1 and Y-P30 peptides are secreted, having been identified in sweat and cell culture medium, respectively (Cunningham et al, 1998;Schittek et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

“…The first product of the dermcidin gene to be identified was proteolysis-inducing factor (PIF), a novel cachectic factor that was purified from a cachexia-inducing murine tumour and the urine of weight-losing patients with pancreatic cancer (Todorov et al, 1996;Wigmore et al, 2000). Screening of tissues for PIF binding demonstrated substantial binding only to skeletal muscle and liver (unpublished observation), and we have investigated the effect of PIF on liver cells.…”

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confidence: 99%

Dermcidin expression in hepatic cells improves survival without N-glycosylation, but requires asparagine residues

et al. 2006

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Proteolysis-inducing factor, a cachexia-inducing tumour product, is an N-glycosylated peptide with homology to the unglycosylated neuronal survival peptide Y-P30 and a predicted product of the dermcidin gene, a pro-survival oncogene in breast cancer. We aimed to investigate whether dermcidin is pro-survival in liver cells, in which proteolysis-inducing factor induces catabolism, and to determine the role of potentially glycosylated asparagine residues in this function. Reverse cloning of proteolysis-inducing factor demonstrated B100% homology with the dermcidin cDNA. This cDNA was cloned into pcDNA3.1 þ and both asparagine residues removed using site-directed mutagenesis. In vitro translation demonstrated signal peptide production, but no difference in molecular weight between the products of native and mutant vectors. Immunocytochemistry of HuH7 cells transiently transfected with V5-His-tagged dermcidin confirmed targeting to the secretory pathway. Stable transfection conferred protection against oxidative stress. This was abrogated by mutation of both asparagines in combination, but not by mutation of either asparagine alone. These findings suggest that dermcidin may function as an oncogene in hepatic as well as breast cells. Glycosylation does not appear to be required, but the importance of asparagine residues suggests a role for the proteolysis-inducing factor core peptide domain.

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“…The identification of proteolysis-inducing factor (PIF) in the urine of cachectic patients, and correlation of its presence with weight loss have helped establish PIF as a novel cachectic factor in humans (Todorov et al, 1996a;Wigmore et al, 2000). However, these studies have been criticised because the authors identified PIF only in the urine and not in the serum (Gullu and Marangoz, 1999).…”

Section: Discussionmentioning

confidence: 99%

Proteolysis-inducing factor is expressed in tumours of patients with gastrointestinal cancers and correlates with weight loss

et al. 2001

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Proteolysis-inducing factor (PIF), a novel cachectic factor, is detectable in the urine of cancer patients experiencing weight loss. We report the expression of PIF in gastrointestinal cancers, and a correlation between PIF expression in tumours, its detection in urine and weight-loss. These data provide the first direct evidence that tumours are the source of PIF in humans. © 2001 Cancer Research Campaign http://www.bjcancer.com

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Characteristics of patients with pancreatic cancer expressing a novel cancer cachectic factor

Abstract: PIF is associated with an accelerated rate of weight loss in patients with a tumour of the pancreatic head. This observation appears to be independent of the effect of an increased hepatic acute-phase protein response.

Cited by 111 publications

References 12 publications

Vitronectin and dermcidin serum levels predict the metastatic progression of AJCC I–II early‐stage melanoma

Vitronectin and dermcidin serum levels predict the metastatic progression of AJCC I–II early‐stage melanoma

Dermcidin expression in hepatic cells improves survival without N-glycosylation, but requires asparagine residues

Proteolysis-inducing factor is expressed in tumours of patients with gastrointestinal cancers and correlates with weight loss

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