Differential secretome of pancreatic cancer cells in serum-containing conditioned medium reveals CCT8 as a new biomarker of pancreatic cancer invasion and metastasis

Abstract Background Pancreatic cancer is a malignancy with a very poor prognosis. The emergence of liquid biopsy is expected to achieve accurate early diagnosis through detection of tumor-derived secreted proteins in the blood. Early diagnosis and treatment of pancreatic cancer could help to improve prognosis. Methods The pretreatment approach of samples can have a major effect on downstream analysis. In this study, we used a pair of homologous pancreatic cancer cell supernatants with different capacities for invasion and metastasis to examine secreted proteins in the conditioned media without the removal of fetal bovine serum, namely through size exclusion chromatography combined with high-abundance protein affinity chromatography to enrich low-concentration protein, followed by mass spectrometry using triple dimethyl labeling. Identification of proteins was performed using an online public database and western blot. Results Mass spectrometry data revealed 77 proteins with quantitative properties, of which 12 proteins had over a 1.5-fold difference (in the supernatant of the highly invasive pancreatic cancer cell line PC-1.0, the expression of 8 proteins were increased and the expression of 4 proteins were decreased). Bioinformatics analysis results showed that CCT8, CTSL, SAA1, IGF2 are secreted via the exosome pathway. According to the literature, with the exception of CCT8, the other three proteins can be detected in blood samples of pancreatic cancer patients, and they can be used as prognostic markers. Western blot results were used to validate consistency with MS results. Conclusion This study found that CCT8 can be used as a liquid biopsy marker to assess the prognosis of pancreatic cancer patients.

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MicroRNA-301a promotes pancreatic cancer invasion and metastasis through the JAK/STAT3 signaling pathway by targeting SOCS5

Carcinogenesis ◽

10.1093/carcin/bgz121 ◽

2019 ◽

Vol 41 (4) ◽

pp. 502-514 ◽

Cited By ~ 9

Author(s):

Hui Hu ◽

Qin Zhang ◽

Weiqun Chen ◽

Tangwei Wu ◽

Shuiyi Liu ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cancer Patients ◽

Cancer Cell ◽

Cell Invasion ◽

Pancreatic Cancer Cell ◽

Cancer Invasion ◽

Janus Kinase ◽

Cancer Cell Invasion ◽

Invasion And Metastasis ◽

And Migration

AbstractPancreatic cancer is one of the most lethal digestive malignant tumors. We had previously found that microRNA-301a (miR-301a) is a oncogenic microRNA whose recognized conduce to nuclear factor-kappa B (NF-κB) activation in pancreatic cancer, yet the underlying mechanisms of miR-301a in promoting pancreatic cancer invasion and migration is obscure. In this work we found that high expression of miR-301a in human pancreatic cancer patients is related to poor survival. Overexpression of miR-301a enhances pancreatic cancer cell invasion, angiogenesis and migration, whereas inhibition of miR-301a suppresses pancreatic cancer cell invasion and reduces orthotopic pancreatic tumor growth and metastasis. Furthermore, suppressor of cytokine signaling 5 (SOCS5) is identified as a target gene of miR-301a. We found that miR-301a suppressed the expression of SOCS5 leads to janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) activation and is related to poor overall survival of pancreatic cancer patients. Taken together, our data show for the first time that the feedback loop between miR-301a and JAK/STAT3 pathway may play a significant role in pancreatic cancer invasion and metastasis. Targeting the loop may prove beneficial to prevent metastasis and provide a more effective therapeutic strategy for pancreatic cancer.

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P10. Effects of bone sialoprotein on pancreatic cancer cell growth, invasion and metastasis

European Journal of Cancer Supplements ◽

10.1016/j.ejcsup.2006.04.070 ◽

2006 ◽

Vol 4 (6) ◽

pp. 30-31

Author(s):

Hany Kayed ◽

Jörg Kleeff ◽

Shereen Keleg ◽

Klaus Felix ◽

Thomas Giese ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cell Growth ◽

Cancer Cell ◽

Pancreatic Cancer Cell ◽

Bone Sialoprotein ◽

Invasion And Metastasis ◽

Cancer Cell Growth

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3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors reduce human pancreatic cancer cell invasion and metastasis

Gastroenterology ◽

10.1053/gast.2002.31093 ◽

2002 ◽

Vol 122 (2) ◽

pp. 308-317 ◽

Cited By ~ 128

Author(s):

Toshiyuki Kusama ◽

Mutsuko Mukai ◽

Teruo Iwasaki ◽

Masaharu Tatsuta ◽

Yoshirou Matsumoto ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cancer Cell ◽

Cell Invasion ◽

Pancreatic Cancer Cell ◽

Coenzyme A ◽

Human Pancreatic Cancer ◽

Cancer Cell Invasion ◽

Human Pancreatic Cancer Cell ◽

Invasion And Metastasis ◽

Reductase Inhibitors

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Prediction of gemcitabine resistance in patients with pancreatic cancer

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.4125 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 4125-4125

Author(s):

S. Nakahira ◽

S. Nakamori ◽

M. Tsujie ◽

J. Okami ◽

I. Takemasa ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cancer Patients ◽

Cancer Cell ◽

Pancreatic Cancer Cell ◽

Human Pancreatic Cancer ◽

Clinical Effects ◽

Resistant Variant ◽

Altered Expression ◽

Gemcitabine Resistance ◽

Recurrent Pancreatic Cancer

4125 Background: Pancreatic cancer is the most lethal of all solid tumors partially because of its chemoresistance. Although a deoxycytidine analogue, gemcitabine, is widely used as a first selected and a single agent for the treatment of this disease despite low response rate, molecular mechanisms of gemcitabine resistance in pancreatic cancer still remain obscure. The purpose of this study is to identify the molecular marker for gemcitabine resistance in human pancreatic cancer. Methods: Gemcitabine resistant variants were established from human pancreatic cancer cell lines, MiaPaCa2. Gene expression changes between parental cells and resistant cells were assessed by an oligonucleotide microarray covering 30,000 human oligonucleotides, and candidate genes were validated by RT-PCR and Western blotting. The association to resistance was validated by RNAi assay. Clinical effects on 18 recurrent pancreatic cancer patients treated by gemcitabine were evaluated using mRNA of specimens resected at the primary operation. Results: The 81-fold gemcitabine resistant variant MiaPaCa2-RG was selected from pancreatic cancer cell line MiaPaCa2. By microarray analysis between parental and resistant MiaPaCa2 cells, 99.6% genes were altered expression of less than 2-fold. Among 43 genes with altered expression of more than 2-fold, the most up-regulated gene in MiaPaCa2-RG cells is ribonucleotide reductase M1 subunit (RRM1) with 4.5-fold up-regulation compared with MiaPaCa2 cells. Transfection with RRM1-specific RNAi suppressed more than 90% of RRM1 mRNA and protein expression both in MiaPaCa2 and MiaPaCa2-RG cells. After RRM1-specific RNAi transfection, gemcitabine chemoresistance of MiaPaCa2-RG was significantly reduced to the same level of MiaPaCa2. The 18 recurrent pancreatic cancer patients were divided into two groups by RRM1 mRNA expression levels. There was a significant association between gemcitabine response and RRM1 expression (p = 0.018). Furthermore, patients with high RRM1 levels had a poor survival times after gemcitabine treatment than those with low RRM1 levels (p = 0.016). Conclusions: RRM1 should be a key molecule in gemcitabine resistance in pancreatic cancer through both in vitro and clinical models. RRM1 should be considered as the predictor of gemcitabine resistance. No significant financial relationships to disclose.

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Role of Motility Factor Released by SW1990 Pancreatic Cancer Cell in Invasion and Metastasis.

The Japanese Journal of Gastroenterological Surgery ◽

10.5833/jjgs.27.2413 ◽

1994 ◽

Vol 27 (11) ◽

pp. 2413-2418

Author(s):

Tetsuji Sawada ◽

Yong-Suk Chung ◽

Toyoshi Sogabe ◽

Nobuya Yamada ◽

Yuichi Arimoto ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cancer Cell ◽

Pancreatic Cancer Cell ◽

Invasion And Metastasis ◽

Motility Factor

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Cytokine modulation of pancreatic cancer cell growth, invasion and metastasis

Gastroenterology ◽

10.1016/s0016-5085(01)81729-7 ◽

2001 ◽

Vol 120 (5) ◽

pp. A347-A348

Author(s):

R ESSNER ◽

M KOJIMA ◽

Y HUNYH ◽

M KELLEY

Keyword(s):

Pancreatic Cancer ◽

Cell Growth ◽

Cancer Cell ◽

Pancreatic Cancer Cell ◽

Invasion And Metastasis ◽

Cancer Cell Growth ◽

Cytokine Modulation

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Detection of Pancreatic Cancer Biomarkers Using Mass Spectrometry

Cancer Informatics ◽

10.4137/cin.s16341 ◽

2014 ◽

Vol 13s7 ◽

pp. CIN.S16341

Author(s):

Kiyoun Kim ◽

Soohyun Ahn ◽

Johan Lim ◽

Byong Chul Yoo ◽

Jin-Hyeok Hwang ◽

...

Keyword(s):

Mass Spectrometry ◽

Pancreatic Cancer ◽

Early Diagnosis ◽

Cancer Patients ◽

Surgical Resection ◽

Missing Values ◽

Survival Rates ◽

Classification Methods ◽

Increased Risk ◽

Patients With Diabetes

Background Pancreatic cancer is the fourth leading cause of cancer-related deaths. Therefore, in order to improve survival rates, the development of biomarkers for early diagnosis is crucial. Recently, diabetes has been associated with an increased risk of pancreatic cancer. The aims of this study were to search for novel serum biomarkers that could be used for early diagnosis of pancreatic cancer and to identify whether diabetes was a risk factor for this disease. Methods Blood samples were collected from 25 patients with diabetes (control) and 93 patients with pancreatic cancer (including 53 patients with diabetes), and analyzed using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF/MS). We performed preprocessing, and various classification methods with imputation were used to replace the missing values. To validate the selection of biomarkers identified in pancreatic cancer patients, we measured biomarker intensity in pancreatic cancer patients with diabetes following surgical resection and compared our results with those from control (diabetes-only) patients. Results By using various classification methods, we identified the commonly splitting protein peaks as m/z 1,465, 1,206, and 1,020. In the follow-up study, in which we assessed biomarkers in pancreatic cancer patients with diabetes after surgical resection, we found that the intensities of m/z at 1,465, 1,206, and 1,020 became comparable with those of diabetes-only patients.

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