Biochemical and Biophysical Research Communications
S100A4, frequently overexpressed in various human cancers, accelerates cell motility in pancreatic cancer cells
Highlights
► We analyzed the effects of forced expression of S100A4 in pancreatic cancer cell lines. ► Cell migration was accelerated after forced expression of S100A4. ► Candidate downstream genes were selected by microarray analysis. ► IFI27 was found to be one of the important downstream genes of S100A4.
Introduction
Pancreatic cancer is one of the most life-threatening diseases, and its invasive capacity and metastatic potential are crucial causes for the difficulty and/or impossibility of surgical resection. In addition, pancreatic cancers are largely resistant to both chemotherapy and radiation therapy. Diagnosis at the early stages of the disease is difficult because this disease does not show any particular symptoms. Therefore, most patients are diagnosed at an advanced disease stage, resulting in a poor prognosis [1]. Establishment of more effective methods for both diagnosis and treatment are necessary for improving the prognoses of pancreatic cancer patients. Curative treatments are limited by invasion and metastasis in many patients; thus, elucidation of molecular pathways is particularly important.
Recently, overexpression of S100A4 in various tumors has been reported [2], and its function as one of the key players in metastatic process has been gradually elucidated [3]. The S100 family members are Ca2+-binding proteins characterized by the EF-hand motif. Twenty-one different human S100 genes have been identified; most of the family member genes are clustered in chromosome 1q21. The physiological properties of these S100 proteins implicate their involvement in diverse cellular functions, including cell proliferation, differentiation, metabolism, motility, and signal transduction; therefore, targeting these molecules should be an effective strategy for cancer therapy [4]. We previously demonstrated the frequent overexpression of S100A4 in pancreatic cancer cell lines; siRNA-mediated knockdown of S100A4 suppressed cell proliferation and invasiveness in only those pancreatic cancer cell lines with a high level of S100A4 expression [5]. Hence it is of great interest to analyze the changes after the introduction of S100A4 into pancreatic cancer cells with low-level expression. Herein we report that cell motility is activated by induction of S100A4 in human pancreatic cancer.
Section snippets
Pancreatic cancer cell lines and culture conditions
In this study, pancreatic cancer cell lines Panc-1, BxPC-3, MIA PaCa-2, AsPC-1, PK-1, PK-8, PK-9, PK-45P, PK-45H, PK-59, PCI-35, PCI-43, PCI-64, PAN-03-JCK, PAN-07-JCK, and PAN-08-JCK were used. The first four cell lines were purchased from American Type Culture Collection (Manassas, VA), and the remaining 12 were obtained from the original developers; they were analyzed in our previous report [5]. The immortalized normal human pancreatic ductal epithelial cell, HPDE [6], was kindly provided by
Expression analyses of S100A4 before and after the introduction by RT-PCR and Western blotting
An association between poor prognosis and S100A4 overexpression has been reported in a variety of cancers, including pancreatic cancer [2]. We first examined the expression of S100A4 in 16 pancreatic cancer cell lines as well as in HPDE, an immortalized normal human pancreatic ductal epithelial cell line, and the results as shown in Supplementary Fig. 1 were in good agreement with our previous report [5]. Then we selected PCI-43 and PCI-35 as the representative cell lines without overexpression
Acknowledgments
We are grateful to Dr. B. L. S. Pierce (University of Maryland University College) for editorial work in the preparation of this manuscript and to Biomedical Research Core (Tohoku University School of Medicine) for technical support. This work was supported in part by Grants-in-Aid (Grant # 17015003, 22591512, and 23590452) and by the Academic Frontier Project for Private Universities: matching fund subsidy 2006–2010 from the Ministry of Education, Culture, Sports, Science and Technology of
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