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ADAM8 expression is associated with increased invasiveness and reduced patient survival in pancreatic cancer.

Valkovskaya N, Kayed H, Felix K, Hartmann D, Giese NA, Osinsky SP, Friess H, Kleeff J - J. Cell. Mol. Med. (2007 Sep-Oct)

Bottom Line: ADAM8 mRNA was significantly overexpressed in pancreatic ductal adenocarcinoma (PDAC) compared with normal pancreatic tissues (5.3-fold increase; P= 0.0008), and high ADAM8 mRNA and protein expression levels correlated with reduced survival time of PDAC patients (P= 0.048 and P= 0.065, respectively).In addition, decreased proteolytic activity was measured in cell culture supernatants following silencing of ADAM8.In conclusion, ADAM8 is overexpressed in PDAC, influences cancer cell invasiveness and correlates with reduced survival, suggesting that ADAM8 might be a potential target in pancreatic cancer therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, University of Heidelberg, Heidelberg, Germany.

ABSTRACT
ADAM8 belongs to a family of transmembrane proteins implicated in cell-cell interactions, proteolysis of membrane proteins, and various aspects of carcinogenesis. In the present study, we aimed to evaluate the expression and function of ADAM8 in pancreatic cancer. ADAM8 mRNA levels were analysed by quantitative RT-PCR and correlated to patient survival. Immunohistochemistry was performed to localize ADAM8 in pancreatic tis-sues. Silencing of ADAM8 expression was carried out by transfection with specific siRNA oligonucleotides. Cell growth and invasion assays were used to assess the functional consequences of ADAM8 silencing. SELDI-TOF-MS was performed to detect the proteolytic activity of ADAM8 in pancreatic cancer cells. ADAM8 mRNA was significantly overexpressed in pancreatic ductal adenocarcinoma (PDAC) compared with normal pancreatic tissues (5.3-fold increase; P= 0.0008), and high ADAM8 mRNA and protein expression levels correlated with reduced survival time of PDAC patients (P= 0.048 and P= 0.065, respectively). Silencing of ADAM8 expression did not significantly influence pancreatic cancer cell growth but suppressed invasiveness. In addition, decreased proteolytic activity was measured in cell culture supernatants following silencing of ADAM8. In conclusion, ADAM8 is overexpressed in PDAC, influences cancer cell invasiveness and correlates with reduced survival, suggesting that ADAM8 might be a potential target in pancreatic cancer therapy.

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Related in: MedlinePlus

ADAM8 expression in pancreatic tissues and serum release. (A) Box and whisker diagram showing ADAM8 mRNA levels in the normal pancreas (n = 20), chronic pancreatitis (n = 28) and pancreatic cancer tissues (n = 68) were assessed by real-time QRT-PCR as described in the ‘Materials and methods’ section. The values are normalized to housekeeping genes (cyclophilin B and HRPT). (B) Survival curves of PDAC patients (n = 64) with low (<30 copies/μl cDNA) and high (≥30 copies/μl cDNA). (C) Serum levels of ADAM8 in patients and healthy controls. The ELISA analysis was performed for 28 serum samples in each examined group, and the results are presented as single values and median (horizontal line).
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fig02: ADAM8 expression in pancreatic tissues and serum release. (A) Box and whisker diagram showing ADAM8 mRNA levels in the normal pancreas (n = 20), chronic pancreatitis (n = 28) and pancreatic cancer tissues (n = 68) were assessed by real-time QRT-PCR as described in the ‘Materials and methods’ section. The values are normalized to housekeeping genes (cyclophilin B and HRPT). (B) Survival curves of PDAC patients (n = 64) with low (<30 copies/μl cDNA) and high (≥30 copies/μl cDNA). (C) Serum levels of ADAM8 in patients and healthy controls. The ELISA analysis was performed for 28 serum samples in each examined group, and the results are presented as single values and median (horizontal line).

Mentions: First QRT-PCR was performed to evaluate the expression of ADAM8 mRNA in normal pancreatic tissue samples (n = 20), chronic pancreatitis (CP) samples (n = 28) and PDAC samples (n = 68). This analysis revealed that the median ADAM8 mRNA levels were significantly higher in PDAC than in normal pancreatic tissues (5.3-fold increase; P= 0.0008). In addition, ADAM8 mRNA levels were also higher in CP samples compared to normal pancreatic tissues (2.4-fold increase; P= 0.032) (Fig. 2A). ADAM8 mRNA levels were 2.2-fold higher in PDAC versus CP tissues;how-ever, this difference was not significant.


ADAM8 expression is associated with increased invasiveness and reduced patient survival in pancreatic cancer.

Valkovskaya N, Kayed H, Felix K, Hartmann D, Giese NA, Osinsky SP, Friess H, Kleeff J - J. Cell. Mol. Med. (2007 Sep-Oct)

ADAM8 expression in pancreatic tissues and serum release. (A) Box and whisker diagram showing ADAM8 mRNA levels in the normal pancreas (n = 20), chronic pancreatitis (n = 28) and pancreatic cancer tissues (n = 68) were assessed by real-time QRT-PCR as described in the ‘Materials and methods’ section. The values are normalized to housekeeping genes (cyclophilin B and HRPT). (B) Survival curves of PDAC patients (n = 64) with low (<30 copies/μl cDNA) and high (≥30 copies/μl cDNA). (C) Serum levels of ADAM8 in patients and healthy controls. The ELISA analysis was performed for 28 serum samples in each examined group, and the results are presented as single values and median (horizontal line).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4401277&req=5

fig02: ADAM8 expression in pancreatic tissues and serum release. (A) Box and whisker diagram showing ADAM8 mRNA levels in the normal pancreas (n = 20), chronic pancreatitis (n = 28) and pancreatic cancer tissues (n = 68) were assessed by real-time QRT-PCR as described in the ‘Materials and methods’ section. The values are normalized to housekeeping genes (cyclophilin B and HRPT). (B) Survival curves of PDAC patients (n = 64) with low (<30 copies/μl cDNA) and high (≥30 copies/μl cDNA). (C) Serum levels of ADAM8 in patients and healthy controls. The ELISA analysis was performed for 28 serum samples in each examined group, and the results are presented as single values and median (horizontal line).
Mentions: First QRT-PCR was performed to evaluate the expression of ADAM8 mRNA in normal pancreatic tissue samples (n = 20), chronic pancreatitis (CP) samples (n = 28) and PDAC samples (n = 68). This analysis revealed that the median ADAM8 mRNA levels were significantly higher in PDAC than in normal pancreatic tissues (5.3-fold increase; P= 0.0008). In addition, ADAM8 mRNA levels were also higher in CP samples compared to normal pancreatic tissues (2.4-fold increase; P= 0.032) (Fig. 2A). ADAM8 mRNA levels were 2.2-fold higher in PDAC versus CP tissues;how-ever, this difference was not significant.

Bottom Line: ADAM8 mRNA was significantly overexpressed in pancreatic ductal adenocarcinoma (PDAC) compared with normal pancreatic tissues (5.3-fold increase; P= 0.0008), and high ADAM8 mRNA and protein expression levels correlated with reduced survival time of PDAC patients (P= 0.048 and P= 0.065, respectively).In addition, decreased proteolytic activity was measured in cell culture supernatants following silencing of ADAM8.In conclusion, ADAM8 is overexpressed in PDAC, influences cancer cell invasiveness and correlates with reduced survival, suggesting that ADAM8 might be a potential target in pancreatic cancer therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, University of Heidelberg, Heidelberg, Germany.

ABSTRACT
ADAM8 belongs to a family of transmembrane proteins implicated in cell-cell interactions, proteolysis of membrane proteins, and various aspects of carcinogenesis. In the present study, we aimed to evaluate the expression and function of ADAM8 in pancreatic cancer. ADAM8 mRNA levels were analysed by quantitative RT-PCR and correlated to patient survival. Immunohistochemistry was performed to localize ADAM8 in pancreatic tis-sues. Silencing of ADAM8 expression was carried out by transfection with specific siRNA oligonucleotides. Cell growth and invasion assays were used to assess the functional consequences of ADAM8 silencing. SELDI-TOF-MS was performed to detect the proteolytic activity of ADAM8 in pancreatic cancer cells. ADAM8 mRNA was significantly overexpressed in pancreatic ductal adenocarcinoma (PDAC) compared with normal pancreatic tissues (5.3-fold increase; P= 0.0008), and high ADAM8 mRNA and protein expression levels correlated with reduced survival time of PDAC patients (P= 0.048 and P= 0.065, respectively). Silencing of ADAM8 expression did not significantly influence pancreatic cancer cell growth but suppressed invasiveness. In addition, decreased proteolytic activity was measured in cell culture supernatants following silencing of ADAM8. In conclusion, ADAM8 is overexpressed in PDAC, influences cancer cell invasiveness and correlates with reduced survival, suggesting that ADAM8 might be a potential target in pancreatic cancer therapy.

Show MeSH
Related in: MedlinePlus