Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2015

Open Access 01-12-2015 | Research article

Dual role of CD44 isoforms in ampullary adenocarcinoma: CD44s predicts poor prognosis in early cancer and CD44ν is an indicator for recurrence in advanced cancer

Authors: Cheng-Lin Wu, Ying-Jui Chao, Ta-Ming Yang, Yi-Ling Chen, Kung-Chao Chang, Hui-Ping Hsu, Yan-Shen Shan, Ming-Derg Lai

Published in: BMC Cancer | Issue 1/2015

Login to get access

Abstract

Background

Although postoperative adjuvant chemoradiotherapies prevent recurrence for some patients with ampullary cancer, the recurrence rate is as high as 29 % in patients with stage I cancer. In an effort to identify predictors of recurrence in patients with ampullary adenocarcinoma, we investigated the clinical value of assessing standard and variant forms of CD44.

Methods

Immunohistochemistry staining and reverse-transcription polymerase chain reaction (RT-PCR) was used to detect standard and variant forms of CD44 in samples of ampullary adenocarcinoma. The cDNA microarray analysis comparing tumors with or without pancreatic invasion was undertaken and analyzed by Ingenuity Pathway Analysis.

Results

The standard CD44 (CD44s) isoform was detected in 76 of 98 patients with ampullary adenocarcinoma, and the negative or weak expression of CD44s was correlated with pancreatic invasion, lymphovascular invasion, advanced stage and bone metastasis. Moderate to dense expression of CD44s was correlated with shorter overall survival in patients with localized cancer (T1 or T2 disease, P = 0.0268). The patients with advanced cancer (T3 or T4 disease) and moderate or dense CD44s expression had a trend toward better survival. Alternative splicing of CD44 was confirmed using RT-PCR, which revealed that the CD44ν3-10 isoform was only expressed in patients with cancer recurrence. Fold change of CD44ν6-10 was also increased. In addition, networks containing CD44, vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), transforming growth factor-β (TGF-β), matrix metalloproteinase 2 (MMP2), AKT, extracellular signal-regulated protein kinase 1 and 2 (ERK1/2), p38 MAPK, activated protein 1 (AP1)‚ and CTNNB1 were constructed after comparing microarray data from patients with and without pancreatic invasion.

Conclusions

Whereas CD44s functions as tumor-promoting oncoprotein in early localized ampullary adenocarcinoma, CD44 variants are expressed in advanced cancer and patients with recurrence. Regional invasiveness and distant metastasis of ampullary cancer is controlled by a complex interacting network.
Appendix
Available only for authorised users
Literature
1.
O’Connell JB, Maggard MA, Manunga J, Tomlinson JS, Reber HA, Ko CY, et al. Survival after resection of ampullary carcinoma: a national population-based study. Ann Surg Oncol. 2008;15:1820–7.CrossRefPubMed
2.
Albores-Saavedra J, Schwartz AM, Batich K, Henson DE. Cancers of the ampulla of Vater: demographics, morphology, and survival based on 5,625 cases from the seer program. J Surg Oncol. 2009;100:598–605.CrossRefPubMed
3.
Hsu HP, Yang TM, Hsieh YH, Shan YS, Lin PW. Predictors for patterns of failure after pancreaticoduodenectomy in ampullary cancer. Ann Surg Oncol. 2007;14:50–60.CrossRefPubMed
4.
Carter JT, Grenert JP, Rubenstein L, Stewart L, Way LW. Tumors of the ampulla of Vater: histopathologic classification and predictors of survival. J Am Coll Surg. 2008;207:210–8.CrossRefPubMed
5.
Palta M, Patel P, Broadwater G, Willett C, Pepek J, Tyler D, et al. Carcinoma of the ampulla of Vater: patterns of failure following resection and benefit of chemoradiotherapy. Ann Surg Oncol. 2012;19:1535–40.CrossRefPubMed
6.
Hsu HP, Shan YS, Hsieh YH, Yang TM, Lin PW. Predictors of recurrence after pancreaticoduodenectomy in ampullary cancer: comparison between non-, early and later recurrence. J Formos Med Assoc. 2007;106:432–43.CrossRefPubMed
7.
Lee JC, Lin PW, Lin YJ, Lai J, Yang HB, Lai MD. Analysis of K-ras gene mutations in periampullary cancers, gallbladder cancers and cholangiocarcinomas from paraffin-embedded tissue sections. J Formos Med Assoc. 1995;94:719–23.PubMed
8.
Hsu HP, Shan YS, Jin YT, Lai MD, Lin PW. Loss of E-cadherin and β-catenin is correlated with poor prognosis of ampullary neoplasms. J Surg Oncol. 2010;101:356–62.PubMed
9.
Hsu HP, Shan YS, Lai MD, Lin PW. Osteopontin-positive infiltrating tumor-associated macrophages in bulky ampullary cancer predict survival. Cancer Biol Ther. 2010;10:144–54.CrossRefPubMed
10.
Dewi DL, Ishii H, Kano Y, Nishikawa S, Haraguchi N, Sakai D, et al. Cancer stem cell theory in gastrointestinal malignancies: recent progress and upcoming challenges. J Gastroenterol. 2011;46:1145–57.CrossRefPubMed
11.
12.
Baumhoer D, Riener MO, Zlobec I, Tornillo L, Vogetseder A, Kristiansen G, et al. Expression of CD24, P-cadherin and S100A4 in tumors of the ampulla of Vater. Mod Pathol. 2009;22:306–13.CrossRefPubMed
13.
Piscuoglio S, Lehmann FS, Zlobec I, Tornillo L, Dietmaier W, Hartmann A, et al. Effect of EpCAM, CD44, CD133 and CD166 expression on patient survival in tumours of the ampulla of Vater. J Clin Pathol. 2012;65:140–5.CrossRefPubMed
14.
Cho SH, Park YS, Kim HJ, Kim CH, Lim SW, Huh JW, et al. CD44 enhances the epithelial-mesenchymal transition in association with colon cancer invasion. Int J Oncol. 2012;41:211–8.PubMed
15.
Dallas MR, Liu G, Chen WC, Thomas SN, Wirtz D, Huso DL, et al. Divergent roles of CD44 and carcinoembryonic antigen in colon cancer metastasis. FASEB J. 2012;26:2648–56.CrossRefPubMedPubMedCentral
16.
Herrlich P, Morrison H, Sleeman J, Orian-Rousseau V, König H, Weg-Remers S, et al. CD44 acts both as a growth- and invasiveness-promoting molecule and as a tumor-suppressing cofactor. Ann N Y Acad Sci. 2000;910:106–20.CrossRefPubMed
17.
Fox SB, Fawcett J, Jackson DG, Collins I, Gatter KC, Harris AL, et al. Normal human tissue, in addition to some tumors, express multiple different CD44 isoforms. Cancer Res. 1994;54:4539–46.PubMed
18.
Zöller M. CD44: can a cancer-initiating cell profit from an abundantly expressed molecule? Nat Rev Cancer. 2011;11:254–67.CrossRefPubMed
19.
Saito S, Okabe H, Watanabe M, Ishimoto T, Iwatsuki M, Baba Y, et al. CD44v6 expression is related to mesenchymal phenotype and poor prognosis in patients with colorectal cancer. Oncol Rep. 2013;29:1570–8.PubMed
20.
Omara-Opyene AL, Qiu J, Shah GV, Iczkowski KA. Prostate cancer invasion is influenced more by expression of a CD44 isoform including variant 9 than by Muc18. Lab Invest. 2004;84:894–907.CrossRefPubMed
21.
Yokoyama Y, Hiyama E, Murakami Y, Matsuura Y, Yokoyama T. Lack of CD44 variant 6 expression in advanced extrahepatic bile duct/ampullary carcinoma. Cancer. 1999;86:1691–9.CrossRefPubMed
22.
Bosman FT, Carneiro F, Hruban RH, Theise ND, WHO Classification of Tumours of the Digestive System. Invasive adenocarcinoma of the ampullary region. In: Albores Saavedra J, Hruban RH, Klimstra DS, Zamboni G, editors. International agency for research on cancer. Lyon: WHO Publications Centre; 2010. p. 87–91.
23.
Van Weering DH, Baas PD, Bos JL. A PCR-based method for the analysis of human CD44 splice products. PCR Methods Appl. 1993;3:100–6.CrossRefPubMed
24.
Hsu KH, Tsai HW, Lin PW, Hsu YS, Shan YS, Lu PJ. Clinical implication and mitotic effect of CD44 cleavage in relation to osteopontin/CD44 interaction and dysregulated cell cycle protein in gastrointestinal stromal tumor. Ann Surg Oncol. 2010;17:2199–212.CrossRefPubMed
25.
Yang K, Tang Y, Habermehl GK, Iczkowski KA. Stable alterations of CD44 isoform expression in prostate cancer cells decrease invasion and growth and alter ligand binding and chemosensitivity. BMC Cancer. 2010;10(16):e1–e12.
26.
Bai Y, Liu YJ, Wang H, Xu Y, Stamenkovic I, Yu Q. Inhibition of the hyaluronan-CD44 interaction by merlin contributes to the tumor-suppressor activity of merlin. Oncogene. 2007;26:836–50.CrossRefPubMed
27.
Katoh M. Networking of WNT, FGF, Notch, BMP, and Hedgehog signaling pathways during carcinogenesis. Stem Cell Rev. 2007;3:30–8.CrossRefPubMed
28.
Descot A, Oskarsson T. The molecular composition of the metastatic niche. Exp Cell Res. 2013;319:1679–86.CrossRefPubMed
29.
Li L, Qi L, Liang Z, Song W, Liu Y, Wang Y, et al. Transforming growth factor-β1 induces EMT by the transactivation of epidermal growth factor signaling through HA/CD44 in lung and breast cancer cells. Int J Mol Med. 2015. doi:10.​3892/​ijmm.​2015.​2222.
30.
Robbins EW, Travanty EA, Yang K, Iczkowski KA. MAP kinase pathways and calcitonin influence CD44 alternate isoform expression in prostate cancer cells. BMC Cancer. 2008;8:260. e1-e9.CrossRefPubMedPubMedCentral
31.
Yoshida GJ, Saya H. Inversed relationship between CD44 variant and c-Myc due to oxidative stress-induced canonical Wnt activation. Biochem Biophys Res Commun. 2014;443:622–7.CrossRefPubMed
Metadata
Title
Dual role of CD44 isoforms in ampullary adenocarcinoma: CD44s predicts poor prognosis in early cancer and CD44ν is an indicator for recurrence in advanced cancer
Authors
Cheng-Lin Wu
Ying-Jui Chao
Ta-Ming Yang
Yi-Ling Chen
Kung-Chao Chang
Hui-Ping Hsu
Yan-Shen Shan
Ming-Derg Lai
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1924-3

Other articles of this Issue 1/2015

BMC Cancer 1/2015 Go to the issue

Research article

A randomized trial of a minimal intervention for sexual concerns after cancer: a comparison of self-help and professionally delivered modalities

Research article

Small ubiquitin-related modifier 2/3 interacts with p65 and stabilizes it in the cytoplasm in HBV-associated hepatocellular carcinoma

Research article

Relationship between body mass index and the expression of hormone receptors or human epidermal growth factor receptor 2 with respect to breast cancer survival

Research article

Methylation-associated Has-miR-9 deregulation in paclitaxel- resistant epithelial ovarian carcinoma

Research article

Multiple primary malignancies involving lung cancer

Research article

Prognostic factors and treatment outcomes in patients with Small Bowel Adenocarcinoma (SBA): The Royal Marsden Hospital (RMH) experience
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits