Cathepsin B is highly expressed in pancreatic cancer stem-like cells and is associated with patients' surgical outcomes

被引:18
作者
Fujimoto, Takuya [1 ]
Tsunedomi, Ryouichi [1 ]
Matsukuma, Satoshi [1 ]
Yoshimura, Kiyoshi [2 ]
Oga, Atsunori [3 ]
Fujiwara, Nobuyuki [1 ]
Fujiwara, Yasuhiro [1 ]
Matsui, Hiroto [1 ]
Shindo, Yoshitaro [1 ]
Tokumitsu, Yukio [1 ]
Suzuki, Nobuaki [1 ]
Kobayashi, Shogo [4 ]
Hazama, Shoichi [5 ]
Eguchi, Hidetoshi [4 ]
Nagano, Hiroaki [1 ]
机构
[1] Yamaguchi Univ, Dept Gastroenterol Breast & Endocrine Surg, Grad Sch Med, 1-1-1 Minami Kogushi, Ube, Yamaguchi 7558505, Japan
[2] Showa Univ, Dept Clin Res Tumor Immunol, Clin Res Inst Clin Pharmacol & Therapeut, Setagaya Ku, Tokyo 1578577, Japan
[3] Yamaguchi Univ, Dept Mol Pathol, Grad Sch Med, Ube, Yamaguchi 7558505, Japan
[4] Osaka Univ, Dept Gastroenterol Surg, Grad Sch Med, Suita, Osaka 5650871, Japan
[5] Yamaguchi Univ, Dept Translat Res & Dev Therapeut Canc, Sch Med, Ube, Yamaguchi 7558505, Japan
关键词
pancreatic cancer; cancer stem cells; biomarker; cathepsin B; GASTRIC-CANCER; TUMOR-GROWTH; INVASION; OVEREXPRESSION; TRANSCRIPTION; ACTIVATION; PROTEOMICS; PROTEASES; FEATURES; ROLES;
D O I
10.3892/ol.2020.12291
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Cancer stem-like cells (CSLCs) in solid tumors are resistant to conventional chemotherapy and molecularly targeted therapy, which is thought to contribute to cancer recurrence and metastasis. The present study aimed to identify biomarkers for pancreatic CSLCs (P-CSLCs). Using our previously reported methods, P-CSLC-enriched populations were generated from pancreatic cancer cell lines. The protein expression profiles of these populations were compared with those of parental cells using two-dimensional electrophoresis, tandem mass spectrometry, flow cytometry and immunohistochemistry. Protein expression in surgical specimens was also evaluated for relationships with clinical outcomes. A lysosomal cysteine protease, cathepsin B (CTSB), was significantly upregulated in P-CSLCs compared with that in the parental cells, as shown using western blotting. Flow cytometry analysis also confirmed that CTSB was more highly expressed on the surface of P-CSLCs compared with that on parental cells. Moreover, PCLCs had elevated cellular secretions of CTSB compared with the parental cells. Finally, CTSB expression was evaluated in 69 resected tumor specimens, and high expression was associated with the patients' clinicopathological features and surgical outcomes. The present results suggested that CTSB is a biomarker for poor survival in patients with pancreatic cancer, which is possibly associated with P-CSLCs. This novel biomarker may also have potential as a therapeutic target.
引用
收藏
页码:1 / 9
页数:9
相关论文
共 51 条
[1]   Cathepsin B: Multiple roles in cancer [J].
Aggarwal, Neha ;
Sloane, Bonnie F. .
PROTEOMICS CLINICAL APPLICATIONS, 2014, 8 (5-6) :427-437
[2]   Cathepsin B Is the Driving Force of Esophageal Cell Invasion in a Fibroblast-Dependent Manner [J].
Andl, Claudia D. ;
McCowan, Kelsey M. ;
Allison, Gillian L. ;
Rustgi, Anil K. .
NEOPLASIA, 2010, 12 (06) :485-498
[3]  
[Anonymous], 2010, TNM classification of malignant tumours
[4]   Cytokeratin 7 and cytokeratin 20 expression in colorectal adenocarcinomas [J].
Bayrak, Reyhan ;
Yenidunya, Sibel ;
Haltas, Hacer .
PATHOLOGY RESEARCH AND PRACTICE, 2011, 207 (03) :156-160
[5]   Overexpression of the Ets-1 transcription factor in human breast cancer [J].
Buggy, Y ;
Maguire, TM ;
McGreal, G ;
McDermott, E ;
Hill, ADK ;
O'Higgins, N ;
Duffy, MJ .
BRITISH JOURNAL OF CANCER, 2004, 91 (07) :1308-1315
[6]   The cancer stem cell: premises, promises and challenges [J].
Clevers, Hans .
NATURE MEDICINE, 2011, 17 (03) :313-319
[7]   The biology of the Ets1 proto-oncogene [J].
Jürgen Dittmer .
Molecular Cancer, 2 (1)
[8]   Overexpression of cathepsin B in gastric cancer identified by proteorne analysis [J].
Ebert, MPA ;
Krüger, S ;
Fogeron, ML ;
Lamer, S ;
Chen, J ;
Pross, M ;
Schulz, HU ;
Lage, H ;
Heim, S ;
Roessner, A ;
Malfertheiner, P ;
Röcken, C .
PROTEOMICS, 2005, 5 (06) :1693-1704
[9]   Stemness Is Enhanced in Gastric Cancer by a SET/PP2A/E2F1 Axis [J].
Enjoji, Shuhei ;
Yabe, Ryotaro ;
Tsuji, Shunya ;
Yoshimura, Kazuhiro ;
Kawasaki, Hideyoshi ;
Sakurai, Masashi ;
Sakai, Yusuke ;
Takenouchi, Hiroko ;
Yoshino, Shigefumi ;
Hazama, Shoichi ;
Nagano, Hiroaki ;
Oshima, Hiroko ;
Oshima, Masanobu ;
Vitek, Michael P. ;
Matsuura, Tetsuya ;
Hippo, Yoshitaka ;
Usui, Tatsuya ;
Ohama, Takashi ;
Sato, Koichi .
MOLECULAR CANCER RESEARCH, 2018, 16 (03) :554-563
[10]   Regulation of Beclin 1 Protein Phosphorylation and Autophagy by Protein Phosphatase 2A (PP2A) and Death-associated Protein Kinase 3 (DAPK3) [J].
Fujiwara, Nobuyuki ;
Usui, Tatsuya ;
Ohama, Takashi ;
Sato, Koichi .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2016, 291 (20) :10858-10866