Trophoblast glycoprotein promotes pancreatic ductal adenocarcinoma cell metastasis through Wnt/planar cell polarity signaling

He,Ping; Jiang,Shuheng; Ma,Mingze; Wang,Yang; Li,Rongkun; Fang,Fang; Tian,Guangang; Zhang,Zhigang

doi:10.3892/mmr.2015.3412

July-2015 Volume 12 Issue 1

Full Size Image

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

July-2015 Volume 12 Issue 1

Full Size Image

Article

Trophoblast glycoprotein promotes pancreatic ductal adenocarcinoma cell metastasis through Wnt/planar cell polarity signaling

Authors:
- Ping He
- Shuheng Jiang
- Mingze Ma
- Yang Wang
- Rongkun Li
- Fang Fang
- Guangang Tian
- Zhigang Zhang
View Affiliations / Copyright

Affiliations: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200240, P.R. China
Pages: 503-509
|
Published online on: March 4, 2015

https://doi.org/10.3892/mmr.2015.3412
Expand metrics +

Abstract

Trophoblast glycoprotein (TPBG), a 72 kDa glycoprotein was identified using a monoclonal antibody, which specifically binds human trophoblast. The expression of TPBG in normal tissues is limited; however, it is upregulated in numerous types of cancer. When TPBG is expressed at a high level, this usually indicates a poor clinical outcome. In the present study, it was demonstrated that TPBG was more commonly observed in human pancreatic ductal adenocarcinoma (PDAC) compared with normal pancreatic tissue. Immunohistochemical analysis of PDAC tissue microarrays indicated that the expression of TPBG in PDAC tissues was closely correlated with the tumor‑node‑metastasis stage of the tumor. Silencing of TPBG in PDAC cell lines resulted in a decreased ability of cancer cell migration and invasion. Further investigation demonstrated that the Wnt/planar cell polarity signaling pathway was suppressed, as the expression of Wnt5a and the activation of c‑Jun N‑terminal kinase was inhibited following TPBG knockdown. In conclusion, the present study provided evidence that TPBG is involved in PDAC metastasis, and that TPBG and its associated signaling pathways may be a suitable target for PDAC therapy.

View Figures

View References

1	Vincent A, Herman J, Schulick R, Hruban RH and Goggins M: Pancreatic cancer. Lancet. 378:607–620. 2011. View Article : Google Scholar : PubMed/NCBI
2	Helm JF, Centeno BA, Coppola D, et al: Outcomes following resection of pancreatic adenocarcinoma: 20-year experience at a single institution. Cancer Control. 15:288–294. 2008.PubMed/NCBI
3	Siegel R, Naishadham D and Jemal A: Cancer statistics, 2013. CA Cancer J Clin. 63:11–30. 2013. View Article : Google Scholar : PubMed/NCBI
4	Hole N and Stern PL: A 72 kD trophoblast glycoprotein defined by a monoclonal antibody. Br J Cancer. 57:239–246. 1988. View Article : Google Scholar : PubMed/NCBI
5	Southall PJ, Boxer GM, Bagshawe KD, Hole N, Bromley M and Stern PL: Immunohistological distribution of 5T4 antigen in normal and malignant tissues. Br J Cancer. 61:89–95. 1990. View Article : Google Scholar : PubMed/NCBI
6	Harrop R, Drury N, Shingler W, et al: Vaccination of colorectal cancer patients with modified vaccinia ankara encoding the tumor antigen 5T4 (TroVax) given alongside chemotherapy induces potent immune responses. Clin Cancer Res. 13:4487–4494. 2007. View Article : Google Scholar : PubMed/NCBI
7	Starzynska T, Marsh PJ, Schofield PF, Roberts SA, Myers KA and Stern PL: Prognostic significance of 5T4 oncofetal antigen expression in colorectal carcinoma. Br J Cancer. 69:899–902. 1994. View Article : Google Scholar : PubMed/NCBI
8	Wrigley E, McGown AT, Rennison J, et al: 5T4 oncofetal antigen expression in ovarian carcinoma. Int J Gynecol Cancer. 5:269–274. 1995. View Article : Google Scholar : PubMed/NCBI
9	Naganuma H, Kono K, Mori Y, et al: Oncofetal antigen 5T4 expression as a prognostic factor in patients with gastric cancer. Anticancer Res. 22:1033–1038. 2002.PubMed/NCBI
10	Carsberg CJ, Myers KA and Stern PL: Metastasis-associated 5T4 antigen disrupts cell-cell contacts and induces cellular motility in epithelial cells. Int J Cancer. 68:84–92. 1996. View Article : Google Scholar : PubMed/NCBI
11	Awan A, Lucic MR, Shaw DM, et al: 5T4 interacts with TIP-2/GIPC, a PDZ protein, with implications for metastasis. Biochem Biophys Res Commun. 290:1030–1036. 2002. View Article : Google Scholar : PubMed/NCBI
12	Ma M-Z, Zhuang C, Yang X-M, et al: CTHRC1 acts as a prognostic factor and promotes invasiveness of gastrointestinal stromal tumors by activating Wnt/PCP-Rho signaling. Neoplasia. 16:265–278. 2014. View Article : Google Scholar : PubMed/NCBI
13	Li J, Yang X-M, Wang Y-H, et al: Monoamine oxidase a suppresses hepatocellular carcinoma metastasis by inhibiting the adrenergic system and its transactivation of EGFR signaling. J Hepatol. 60:1225–1234. 2014. View Article : Google Scholar : PubMed/NCBI
14	Weeraratna AT, Jiang Y, Hostetter G, et al: Wnt5a signaling directly affects cell motility and invasion of metastatic melanoma. Cancer Cell. 1:279–288. 2002. View Article : Google Scholar : PubMed/NCBI
15	Yamamoto H, Oue N, Sato A, et al: Wnt5a signaling is involved in the aggressiveness of prostate cancer and expression of metal-loproteinase. Oncogene. 29:2036–2046. 2010. View Article : Google Scholar : PubMed/NCBI
16	Vuga LJ, Ben-Yehudah A, Kovkarova-Naumovski E, et al: WNT5A is a regulator of fibroblast proliferation and resistance to apoptosis. Am J Respir Cell Mol Biol. 41:583–589. 2009. View Article : Google Scholar : PubMed/NCBI
17	Castro FV, McGinn OJ, Krishnan S, et al: 5T4 oncofetal antigen is expressed in high risk of relapse childhood pre-B acute lymphoblastic leukemia and is associated with a more invasive and chemotactic phenotype. Leukemia. 26:1487–1498. 2012. View Article : Google Scholar : PubMed/NCBI
18	Katoh M: WNT/PCP signaling pathway and human cancer (review). Oncol Rep. 14:1583–1588. 2005.PubMed/NCBI
19	Wang Y: Wnt/Planar cell polarity signaling: a new paradigm for cancer therapy. Mol Cancer Ther. 8:2103–2109. 2009. View Article : Google Scholar : PubMed/NCBI
20	Kagermeier-Schenk B, Wehner D, Özhan-Kizil G, et al: Waif1/5T4 inhibits Wnt/β-catenin signaling and activates noncanonical Wnt pathways by modifying LRP6 subcellular localization. Dev Cell. 21:1129–1143. 2011. View Article : Google Scholar : PubMed/NCBI
21	Kurayoshi M, Oue N, Yamamoto H, et al: Expression of Wnt-5a is correlated with aggressiveness of gastric cancer by stimulating cell migration and invasion. Cancer Res. 66:10439–10448. 2006. View Article : Google Scholar : PubMed/NCBI
22	Pukrop T, Klemm F, Hagemann T, et al: Wnt 5a signaling is critical for macrophage-induced invasion of breast cancer cell lines. Proc Natl Acad Sci USA. 103:5454–5459. 2006. View Article : Google Scholar : PubMed/NCBI
23	Oishi I, Suzuki H, Onishi N, et al: The receptor tyrosine kinase Ror2 is involved in non-canonical Wnt5a/JNK signalling pathway. Genes Cells. 8:645–654. 2003. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Trophoblast glycoprotein promotes pancreatic ductal adenocarcinoma cell metastasis through Wnt/planar cell polarity signaling

This article is mentioned in:

Abstract

Figure 1

Figure 2

Figure 3

Figure 4

Related Articles