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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

MMP2 and MMP9 may be downstream effectors of c-MET knockdown, leading to suppression of migration in T24 bladder cancer cells.(A) Wound-healing assay showing that knockdown of c-MET inhibitsthe migration of T24 cells. (B) Loss of c-MET downregulated the expression of matrix metalloproteinases (MMP)-2 and MMP-9. All experiments were performed using two c-MET knockdown cell lines (sic-MET-1 and sic-MET-2) transfected with different MET siRNAs, and two control cell lines (Ctrl and NT). Ctrl, control; NT, non-transfected.
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pone.0134552.g002: MMP2 and MMP9 may be downstream effectors of c-MET knockdown, leading to suppression of migration in T24 bladder cancer cells.(A) Wound-healing assay showing that knockdown of c-MET inhibitsthe migration of T24 cells. (B) Loss of c-MET downregulated the expression of matrix metalloproteinases (MMP)-2 and MMP-9. All experiments were performed using two c-MET knockdown cell lines (sic-MET-1 and sic-MET-2) transfected with different MET siRNAs, and two control cell lines (Ctrl and NT). Ctrl, control; NT, non-transfected.

Mentions: We examined cell migration and MMP2 and MMP9 expression in BCa cells. Wound-healing assay (also called as in vitro scratch assay) showed that c-MET-knockdown cells migrated less efficiently than control cells (Fig 2A). We also found that knocking down c-MET downregulated the expression of MMP2 and MMP9 in BCa cells (Fig 2B).


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)

MMP2 and MMP9 may be downstream effectors of c-MET knockdown, leading to suppression of migration in T24 bladder cancer cells.(A) Wound-healing assay showing that knockdown of c-MET inhibitsthe migration of T24 cells. (B) Loss of c-MET downregulated the expression of matrix metalloproteinases (MMP)-2 and MMP-9. All experiments were performed using two c-MET knockdown cell lines (sic-MET-1 and sic-MET-2) transfected with different MET siRNAs, and two control cell lines (Ctrl and NT). Ctrl, control; NT, non-transfected.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4520492&req=5

pone.0134552.g002: MMP2 and MMP9 may be downstream effectors of c-MET knockdown, leading to suppression of migration in T24 bladder cancer cells.(A) Wound-healing assay showing that knockdown of c-MET inhibitsthe migration of T24 cells. (B) Loss of c-MET downregulated the expression of matrix metalloproteinases (MMP)-2 and MMP-9. All experiments were performed using two c-MET knockdown cell lines (sic-MET-1 and sic-MET-2) transfected with different MET siRNAs, and two control cell lines (Ctrl and NT). Ctrl, control; NT, non-transfected.
Mentions: We examined cell migration and MMP2 and MMP9 expression in BCa cells. Wound-healing assay (also called as in vitro scratch assay) showed that c-MET-knockdown cells migrated less efficiently than control cells (Fig 2A). We also found that knocking down c-MET downregulated the expression of MMP2 and MMP9 in BCa cells (Fig 2B).

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