LAMA4 upregulation is associated with high liver metastasis potential and poor survival outcome of Pancreatic Cancer

Biao Zheng, Jianhua Qu, Kenoki Ohuchida, Haimin Feng, Stephen Jun Fei Chong, Zilong Yan, Yicui Piao, Peng Liu, Nan Sheng, Daiki Eguchi, Ohtsuka Takao, Kazuhiro Mizumoto, Zhong Liu, Shazib Pervaiz, Peng Gong, Masafumi Nakamura

研究成果: Contribution to journalArticle査読

5 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)10274-10289
ページ数16
ジャーナルTheranostics
10
22
DOI
出版ステータス出版済み - 2020

All Science Journal Classification (ASJC) codes

  • 医学(その他)
  • 薬理学、毒性学および薬学(その他)

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