Proteomic analysis of primary esophageal squamous cell carcinoma reveals downregulation of a cell adhesion protein, periplakin

Abstract

Recent advances in two-dimensional electrophoresis (2-DE) such as fluorescent 2-D differential gel electrophoresis (2-D DIGE) has made it possible to detect and quantitate the critical changes involved in disease pathogenesis. We have previously identified novel proteins with altered expression in primary colorectal cancer using agarose 2-DE that has a higher loading capacity than immobilized pH gradient gel. The aim of this study is to identify novel proteins with altered expression in primary esophageal cancer using the powerful method of agarose 2-DE and agarose 2-D DIGE. Excised tissues from 12 patients of primary esophageal cancer were obtained. Proteins with altered expression between cancer and adjacent non-cancer tissues were analyzed by agarose 2-D DIGE and identified by mass spectrometry. Thirty-three proteins out of 74 spots with altered expression in tumors were identified. Among them, a 195-kDa protein, periplakin, was significantly downregulated in esophageal cancer, which was confirmed by immunoblotting. Immunohistochemistry showed that periplakin was mainly localized at cell-cell boundaries in normal epithelium and dysplastic lesions, while it disappeared from cell boundaries, shifted to cytoplasm, in early cancers and scarcely expressed in advanced cancers. These results suggest that periplakin could be a useful marker for detection of early esophageal cancer and evaluation of tumor progression.

Calreticulin promotes cell motility and enhances resistance to anoikis through STAT3–CTTN–Akt pathway in esophageal squamous cell carcinoma

“…CRT may have an important role in the development and/or progression of various human cancers: overexpression of CRT has been found in breast ductal carcinoma (Bini et al, 1997;Chahed et al, 2005), prostate adenocarcinoma (Alaiya et al, 2000), hepatocellular carcinoma (Kim et al, 2004) and colon cancer (Vougas et al, 2008). In ESCC, research by other groups and our previous finding suggests that CRT overexpression is a prevalent event in malignant transformation of esophageal epithelial cells (Nishimori et al, 2006;Du et al, 2007). Importantly, we observed that patients with CRT overexpression presented a shorter survival time compared to those with low CRT expression.…”

Serum Periplakin as a Potential Biomarker for Urothelial Carcinoma of the Urinary Bladder

“…Downregulation of periplakin was correlated with the progression of esophageal squamous cell carcinoma (Hatakeyama et al, 2006;Nishimori et al, 2006). Cyclin A2-induced upregulation of periplakin was associated with poor prognosis as well as cisplatin resistance in endometrial cancer cells (Suzuki et al, 2010).…”

Proteomic Study of Esophageal Squamous Cell Carcinoma

“…Two reports described the proteomic signatures of ESCC with samples from Japan. Nishimori et al used the agarose IEF gel in the first dimension, which not only allows for large-scale quantitative comparisons of protein expression but also is able to resolve high molecular mass proteins larger than 150 kDa [Nishimori et al, 2006]. As a result, a different protein pattern was revealed, including a few protein candidates with MW > 70 kDa.…”

“…↑or ↓ Calcium-dependent phospholipid binding calcium ion binding [Du et al, 2007;Liu et al, 2011] Annexin A8 ↓ [Nishimori et al, 2006] Annexin I ↓or↑ [Du et al, 2007;Jazii et al, 2006;Liu et al, 2011;Nishimori et al, 2006;Zhou et al, 2005;Zhu et al, 2010 [Du et al, 2007;Nishimori et al, 2006] DnaJ(Hsp40) homolog ↑ [Nishimori et al, 2006] www.intechopen.com…”

“…↑or ↓ Transcription regulation [Fu et al, 2007;Qi et al, 2005] Neuronal protein ↑ Neuronal growth [Qi et al, 2005] Nuclear autoantigenic sperm protein isoform 1 ↑ Hsp90 protein binding [Nishimori et al, 2006] Myosin heavy chain nonmuscle form A ↓ Actin binding or calmodulin binding [Nishimori et al, 2006] Caldesmon 1 isoform 1 ↓ [Nishimori et al, 2006] Myosin regulatory light chain 2 ↓ Ventricular/cardiac muscle isoform [Jazii et al, 2006;Zhu et al, 2010] Myosin light chain 2 ↓ Regulatory light chain of myosin [Jazii et al, 2006] [Nishimori et al, 2006] Calponin 1, basic ↓ actin binding ; calmodulin binding [Nishimori et al, 2006] DNA directed RNA polymerase B (ropB) ↑ Transcription [Jazii et al, 2006] GH16431P ↑ NA [Jazii et al, 2006] OPTN protein ↓ Protein C-terminus binding [Fu et al, 2007] 67 kDa laminin receptor ↑ Signal transduction [Fu et al, 2007 [Zhu et al, 2010] Peptidyl-prolyl cis-trans isomerase A ↑ Peptidyl-prolyl cis-trans isomerase activity [Zhu et al, 2010] Cystatin-B ↑ Cysteine-type endopeptidase inhibitor activity [Zhu et al, 2010] Serum amyloid P-component [Precursor] ↓ Protein binding [Zhu et al, 2010] Phosphatidylethanolamine-binding protein1 ↓ Serine-type endopeptidase inhibitor [Zhu et al, 2010] Carbonic anhydrase 1 ↓ Carbonate dehydratase activity [Zhu et al, 2010] Carbonic anhydrase 3 ↓ [Zhu et al, 2010] Creatine kinase M-type ↓ Creatine kinase activity [Zhu et al, 2010] [Ong & Mann, 2006]. We used SILAC medium to label immortalized cells (NE3 and NE6) with heavy stable isotope [U-13 C 6 ]-H-Lysine and [U-13 C 6 ]-H-Arginine and cancer cells (EC1, EC109, EC9706) with light stable isotope [ 12 C 6 ]-L-Lysine and [ 12 C 6 ]-LArginine, respectively.…”