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Title: LAMA4 upregulation is associated with high liver metastasis potential and poor survival outcome of Pancreatic Cancer
Authors: Zheng, B.
Qu, J. 
Ohuchida, K.
Feng, H.
Chong, Stephen Jun Fei 
Yan, Z.
Piao, Y.
Liu, P.
Sheng, N.
Eguchi, D.
Ohtsuka, T.
Mizumoto, K.
Liu, Z.
Pervaiz, S. 
Gong, P.
Nakamura, M.
Keywords: Cancer-associated fibroblasts
Pancreatic cancer
Tumor severity
Issue Date: 2020
Publisher: Ivyspring International Publisher
Citation: Zheng, B., Qu, J., Ohuchida, K., Feng, H., Chong, Stephen Jun Fei, Yan, Z., Piao, Y., Liu, P., Sheng, N., Eguchi, D., Ohtsuka, T., Mizumoto, K., Liu, Z., Pervaiz, S., Gong, P., Nakamura, M. (2020). LAMA4 upregulation is associated with high liver metastasis potential and poor survival outcome of Pancreatic Cancer. Theranostics 10 (22) : 10274-10289. ScholarBank@NUS Repository.
Rights: Attribution-NonCommercial 4.0 International
Abstract: Rationale: Pancreatic cancer is one of the most difficult cancers to manage and its poor prognosis stems from the lack of a reliable early disease biomarker coupled with its highly metastatic potential. Liver metastasis accounts for the high mortality rate in pancreatic cancer. Therefore, a better understanding of the mechanism(s) underlying the acquisition of the metastatic potential in pancreatic cancer is highly desirable. Methods: Microarray analysis in wild-type and highly liver metastatic human pancreatic cancer cell lines was performed to identify gene expression signatures that underlie the metastatic process. We validated our findings in patient samples, nude mice, cell lines and database analysis. Results: We identified a metastasis-related gene, laminin subunit alpha 4 (LAMA4), that was upregulated in highly liver metastatic human pancreatic cancer cell lines. Downregulation of LAMA4 reduced the liver metastatic ability of pancreatic cancer cells in vivo. Furthermore, LAMA4 expression was positively correlated with tumor severity and in silico analyses revealed that LAMA4 was associated with altered tumor microenvironment. In particular, our in vitro and in vivo results showed that LAMA4 expression was highly correlated with cancer-associated fibroblasts (CAFs) level which may contribute to pancreatic cancer metastasis. We further found that LAMA4 had a positive effect on the recruitment and activity of CAFs. Conclusions: These data provide evidence for LAMA4 as a possible biomarker of disease progression and poor prognosis in pancreatic cancer. Our findings indicate that LAMA4 may contribute to pancreatic cancer metastasis via recruitment or activation of CAFs. © 2020 Ivyspring International Publisher. All rights reserved.
Source Title: Theranostics
ISSN: 1838-7640
DOI: 10.7150/thno.47001
Rights: Attribution-NonCommercial 4.0 International
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