Pancreatic Cancer Proteome: The Proteins That Underlie Invasion, Metastasis, and Immunologic Escape

Chen, Ru; Yi, Eugene C.; Donohoe, Samuel; Pan, Sheng; Eng, Jimmy K.; Cooke, Kelly; Crispin, David A.; Lane, Zhaoli; Bronner, Mary P.; Aebersold, Ruedi; Brentnall, Teresa A.

doi:10.1053/j.gastro.2005.08.001

Cited by 170 publications

(145 citation statements)

References 32 publications

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“…16,17 Recently, proteomic and microarray profiling studies showed that periostin is up-regulated in pancreatic cancer tissues. [18][19][20] However, it has been demonstrated that periostin protein was mainly detected in the juxtatumoral stroma components, while the tumor cells themselves showed no immunoreactivity. Consistently, quantitative real-time RT-PCR revealed that periostin was not or very faintly expressed in pancreatic cancer cell lines, but it was strongly expressed in PSC.…”

Section: Discussionmentioning

confidence: 99%

Periostin, secreted from stromal cells, has biphasic effect on cell migration and correlates with the epithelial to mesenchymal transition of human pancreatic cancer cells

Kanno

Satoh

Masamune

et al. 2008

Intl Journal of Cancer

123

103

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Periostin is a secretory protein that has been suggested to function as a cell adhesion molecule and promote the invasiveness or growth rate of tumors. However, little is known about the association of its expression and epithelial to mesenchymal transition (EMT), which is considered to play a crucial role in cancer cell metastasis. Thus, the authors investigated whether periostin could be involved in the process of EMT and the role of this gene in pancreatic cancer development. The expression of periostin was observed mainly in stromal cells but very little in cancer cells by immunohistochemistry and real-time RT-PCR. In vitro, pancreatic stellate cells (PSCs) exhibited a much higher basal expression of periostin compared with cancer cells. Periostin secreted in the supernatant from 293T cells that expressed periostin (approximately 150 ng/ml) inhibited the migration of pancreatic cancer cells. Coculture assay revealed that periostin expression in PSC was induced by pancreatic cancer cells. To assess the direct role of periostin in pancreatic cancer cells, the authors generated pancreatic cancer cell lines that stably express periostin. The induced expression of periostin (to 150 ng/ml) altered the morphology of cancer cells, changing them from mesenchymal to epithelial phenotypes with the induction of epithelial markers and a reduction of mesenchymal markers, and showed reduced cell migration in vitro and formed smaller tumors as well as suppressed metastasis in vivo. On the other hand, high concentration of recombinant periostin (1 lg/ml) promoted cell migration with AKT activation. The findings suggest that periostin has biphasic effect on the development of pancreatic cancer. ' 2008 Wiley-Liss, Inc.Key words: pancreatic cancer; periostin; EMT; pancreatic stellate cell Pancreatic adenocarcinoma is one of the most malignant gastrointestinal tumors. Once pancreatic cancer is clinically evident, it progresses rapidly to develop metastatic lesions, frequently by the time of diagnosis. The pathogenic mechanisms that regulate the aggressive behavior of this cancer still remain to be clarified.Tumor metastasis is a multistep pathological process involved in the final phase of tumor development. During this process, epithelium-derived tumor cells undergo fibroblast-like transformation, referred to as epithelial-mesenchymal transition (EMT). 1,2 EMT is the process by which an epithelial cell shows transitory changes in cell structure and becomes a more motile mesenchymal cell with migratory properties during embryogenesis. This transition is considered to be an important event during malignant tumor progression and metastasis. [3][4][5] Periostin is a secretory protein that has been suggested to function as a cell adhesion molecule for preosteoblasts and to participate in osteoblast recruitment, attachment and spreading. 6,7 Recently, the expression of periostin has been implicated in the development of variety of carcinomas such as neuroblastoma, 8 epithelial ovarian cancer 9 and non-small cell lung carcinoma. 10 P...

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Section: Discussionmentioning

confidence: 99%

Periostin, secreted from stromal cells, has biphasic effect on cell migration and correlates with the epithelial to mesenchymal transition of human pancreatic cancer cells

Kanno

Satoh

Masamune

et al. 2008

Intl Journal of Cancer

123

103

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“…Periostin contains 4 internal repeats sharing a homology with fasciclin I, which leads to the hypothesis that it functions to recruit and attach osteoblasts to the periosteum (25). It has been shown by serial analysis of gene expression (SAGE) and multiple genome-wide microarrays that human periostin gene is overexpressed in several human tumors including carcinomas of ovary, breast, pancreas and head and neck squamous cell carcinoma (26)(27)(28)(29)(30). On the other hand, acquired expression of periostin by cancer cells greatly promotes metastatic development, adhesion and invasion of cancer cell lines (7,8,12,13,15).…”

Section: Discussionmentioning

confidence: 99%

Circulating levels of periostin may help identify patients with more aggressive colorectal cancer

Ben

Zhao²,

Ge³

et al. 2009

Int J Oncol

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Abstract. Elevated levels of periostin have been implicated as playing important roles in tumor invasion and metastasis in various tissues. Thus, we determined whether serum periostin levels were associated with progression and poor prognosis in colorectal cancer (CRC) patients. We measured serum periostin levels by ELISA in 67 CRC patients and 120 controls. We also evaluated periostin expression in human CRC specimens (n=15) using immunohistochemistry, and measured expression of periostin mRNA in 7 CRC tissue samples, matched normal tissues and in 4 colon cancer cell lines by RT-PCR. We analyzed the relationship between serum levels of periostin and other clinicopathologic characteristics in patients with CRC. The serum levels of periostin in CRC patients (40.9±15.4 ng/ml) were significantly elevated compared to that in healthy volunteers (21.0±7.3 ng/ml, P<0.0001) and benign colorectal polyps or adenomas (22.4±8.5 ng/ml, P<0.0001). Higher preoperative serum levels of periostin in CRC were found to correlate with distant metastasis (P=0.003), advanced-stage disease (stage III/IV, P<0.0001) and poor prognosis. Preoperative serum periostin levels of 15 cases were significantly higher than matched postoperative levels (47.2±13.5 ng/ml vs. 31.3±11.0 ng/ml, P=0.008). Twelve of 15 patients (80%) had positive immunohistochemical periostin staining in CRC samples. Interestingly, periostin mRNA was highly upregulated in CRCs in comparison with matched normal tissues, and no expression of periostin mRNA was detected in 4 colon cancer cell lines. Serum levels of periostin detected by ELISA may be of clinical value in identifying patients who may be at high risk for aggression and metastasis of CRC. Periostin may be produced by the stromal cells surrounding the tumor, but not by the CRC cells themselves.

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“…Through a period of suspension culture, epithelial cells were enriched while stromal components were reduced to less than 1%, confirmed by FACS analysis with markers for epithelial (ESA, Ca19.9) and fibroblast (CD73, CD105, CD90) phenotype. The CFPAC-1 cells and normal duct cells were resuspended for 1 hour in lysis buffer consisting of Tris/HCl (50mM, p H 7.4), NaCl (150 mM), Triton X-100 (0.5% w/v), NP-40 (0.5% w/v), 80 mM dithiothreitol (DTT), 10 μL/mL protease inhibitor cocktails (Sigma-Aldrich), 1 mM PMSF, 1 mM Na 3 VO 4 and PhosStop phosphatase inhibitor cocktail (Roche), sonicated for 30 s, and centrifuged at 16,000× g for 10 min. The supernatants were precipitated with 4 volume of acetone (Sigma-Aldrich) overnight at -20°C and centrifuged at 9,000× g for 5 min.…”

Section: Sample Preparationmentioning

confidence: 99%

“…Most patients die within 12 months and only 4% survive for 5 years after diagnosis [1,2]. In the past decade, various mass spectrometry-based approaches have been applied to investigate the proteomes of diseased and normal samples from pancreatic tissues, juice, cell lines, and serum, with the goals of dissecting the abnormal signaling pathways underlying oncogenesis and identifying new biomarkers [3][4][5][6][7][8][9][10][11][12][13]; however, the description of the content of phosphoproteins in pancreatic cancer cells were limited. Since this information archive represents many of the new drug targets for kinase-based inhibitors, it is of critical importance to characterize this molecular information source.…”

Section: Introductionmentioning

confidence: 99%

Phosphoproteomic Analysis of Pancreatic Ductal Adenocarcinoma Cells Reveals Differential Phosphorylation of Cell Adhesion, Cell Junction and Structural Proteins

Zhou

Capello²,

Fredolini

et al. 2011

JPB

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Pancreatic Cancer Proteome: The Proteins That Underlie Invasion, Metastasis, and Immunologic Escape

Cited by 170 publications

References 32 publications

Periostin, secreted from stromal cells, has biphasic effect on cell migration and correlates with the epithelial to mesenchymal transition of human pancreatic cancer cells

Periostin, secreted from stromal cells, has biphasic effect on cell migration and correlates with the epithelial to mesenchymal transition of human pancreatic cancer cells

Circulating levels of periostin may help identify patients with more aggressive colorectal cancer

Phosphoproteomic Analysis of Pancreatic Ductal Adenocarcinoma Cells Reveals Differential Phosphorylation of Cell Adhesion, Cell Junction and Structural Proteins

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