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The c-MET Network as Novel Prognostic Marker for Predicting Bladder Cancer Patients with an Increased Risk of Developing Aggressive Disease.

Kim YW, Yun SJ, Jeong P, Kim SK, Kim SY, Yan C, Seo SP, Lee SK, Kim J, Kim WJ - PLoS ONE (2015)

Bottom Line: In vitro analysis, c-MET knockdown suppressed cell proliferation, invasion, and migration, and increased sensitivity to cisplatin-induced apoptosis.In addition, c-MET network gene (c-MET, AXL, and PDGFR) expression allowed discrimination of BCa tissues from normal control tissues and appeared to predict poor disease progression in non-muscle invasive BCa patients and poor overall survival in muscle invasive BCa patients.These genes might be a useful marker for co-targeting therapy, and are expected to play an important role in improving both response to treatment and survival of BCa patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, College of Medicine, Chungbuk National University, Cheongju, South Korea.

ABSTRACT
Previous studies have shown that c-MET is overexpressed in cases of aggressive bladder cancer (BCa). Identification of crosstalk between c-MET and other RTKs such as AXL and PDGFR suggest that c-MET network genes (c-MET-AXL-PDGFR) may be clinically relevant to BCa. Here, we examine whether expression of c-MET network genes can be used to identify BCa patients at increased risk of developing aggressive disease. In vitro analysis, c-MET knockdown suppressed cell proliferation, invasion, and migration, and increased sensitivity to cisplatin-induced apoptosis. In addition, c-MET network gene (c-MET, AXL, and PDGFR) expression allowed discrimination of BCa tissues from normal control tissues and appeared to predict poor disease progression in non-muscle invasive BCa patients and poor overall survival in muscle invasive BCa patients. These results suggest that c-MET network gene expression is a novel prognostic marker for predicting which BCa patients have an increased risk of developing aggressive disease. These genes might be a useful marker for co-targeting therapy, and are expected to play an important role in improving both response to treatment and survival of BCa patients.

No MeSH data available.


Related in: MedlinePlus

Loss of c-MET reduced anchorage-independent proliferation (A) and invasion (B) of T24 bladder cancer cells with an increased cisplatin-induced cell apoptosis (C).All experiments were performed using three c-MET knockdown cell lines (sic-MET-1, sic-MET-2, and sic-MET-3) transfected with different METsiRNAs, and two controls cell lines (Ctrl and NT). Ctrl, control; NT, non-transfected.*p<0.05.
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pone.0134552.g001: Loss of c-MET reduced anchorage-independent proliferation (A) and invasion (B) of T24 bladder cancer cells with an increased cisplatin-induced cell apoptosis (C).All experiments were performed using three c-MET knockdown cell lines (sic-MET-1, sic-MET-2, and sic-MET-3) transfected with different METsiRNAs, and two controls cell lines (Ctrl and NT). Ctrl, control; NT, non-transfected.*p<0.05.

Mentions: Previous studies suggest that stromal HGF signaling via the c-MET pathway increases invasion and metastasis of BCa cells [6, 11, 13]; therefore, we sought to determine the effects of c-MET silencing on proliferation and invasion, and on the apoptotic response to cisplatin (a major chemotherapeutic agent used to treat BCa patients). We found that the BCa cells in which c-MET was knocked down formed fewer (and smaller) colonies than the negative control cells, suggesting a reduction in cell proliferation in soft agar (Fig 1A). The cell invasion assay showed that BCa cells harboring intact c-MET were more invasive than those in which c-MET was knocked down. c-MET-silenced T24 cells were much less invasive than controls cells (non-transfected cells and cells transfected with control siRNA) (Fig 1B). We next examined the consequence of c-MET loss on cell apoptosis in an MTT assay. c-MET knockdown cells showed increased sensitivity to cisplatin-induced apoptosis (Fig 1C).


The c-MET Network as Novel Prognostic Marker for Predicting Bladder Cancer Patients with an Increased Risk of Developing Aggressive Disease.

Kim YW, Yun SJ, Jeong P, Kim SK, Kim SY, Yan C, Seo SP, Lee SK, Kim J, Kim WJ - PLoS ONE (2015)

Loss of c-MET reduced anchorage-independent proliferation (A) and invasion (B) of T24 bladder cancer cells with an increased cisplatin-induced cell apoptosis (C).All experiments were performed using three c-MET knockdown cell lines (sic-MET-1, sic-MET-2, and sic-MET-3) transfected with different METsiRNAs, and two controls cell lines (Ctrl and NT). Ctrl, control; NT, non-transfected.*p<0.05.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4520492&req=5

pone.0134552.g001: Loss of c-MET reduced anchorage-independent proliferation (A) and invasion (B) of T24 bladder cancer cells with an increased cisplatin-induced cell apoptosis (C).All experiments were performed using three c-MET knockdown cell lines (sic-MET-1, sic-MET-2, and sic-MET-3) transfected with different METsiRNAs, and two controls cell lines (Ctrl and NT). Ctrl, control; NT, non-transfected.*p<0.05.
Mentions: Previous studies suggest that stromal HGF signaling via the c-MET pathway increases invasion and metastasis of BCa cells [6, 11, 13]; therefore, we sought to determine the effects of c-MET silencing on proliferation and invasion, and on the apoptotic response to cisplatin (a major chemotherapeutic agent used to treat BCa patients). We found that the BCa cells in which c-MET was knocked down formed fewer (and smaller) colonies than the negative control cells, suggesting a reduction in cell proliferation in soft agar (Fig 1A). The cell invasion assay showed that BCa cells harboring intact c-MET were more invasive than those in which c-MET was knocked down. c-MET-silenced T24 cells were much less invasive than controls cells (non-transfected cells and cells transfected with control siRNA) (Fig 1B). We next examined the consequence of c-MET loss on cell apoptosis in an MTT assay. c-MET knockdown cells showed increased sensitivity to cisplatin-induced apoptosis (Fig 1C).

Bottom Line: In vitro analysis, c-MET knockdown suppressed cell proliferation, invasion, and migration, and increased sensitivity to cisplatin-induced apoptosis.In addition, c-MET network gene (c-MET, AXL, and PDGFR) expression allowed discrimination of BCa tissues from normal control tissues and appeared to predict poor disease progression in non-muscle invasive BCa patients and poor overall survival in muscle invasive BCa patients.These genes might be a useful marker for co-targeting therapy, and are expected to play an important role in improving both response to treatment and survival of BCa patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, College of Medicine, Chungbuk National University, Cheongju, South Korea.

ABSTRACT
Previous studies have shown that c-MET is overexpressed in cases of aggressive bladder cancer (BCa). Identification of crosstalk between c-MET and other RTKs such as AXL and PDGFR suggest that c-MET network genes (c-MET-AXL-PDGFR) may be clinically relevant to BCa. Here, we examine whether expression of c-MET network genes can be used to identify BCa patients at increased risk of developing aggressive disease. In vitro analysis, c-MET knockdown suppressed cell proliferation, invasion, and migration, and increased sensitivity to cisplatin-induced apoptosis. In addition, c-MET network gene (c-MET, AXL, and PDGFR) expression allowed discrimination of BCa tissues from normal control tissues and appeared to predict poor disease progression in non-muscle invasive BCa patients and poor overall survival in muscle invasive BCa patients. These results suggest that c-MET network gene expression is a novel prognostic marker for predicting which BCa patients have an increased risk of developing aggressive disease. These genes might be a useful marker for co-targeting therapy, and are expected to play an important role in improving both response to treatment and survival of BCa patients.

No MeSH data available.


Related in: MedlinePlus