論文

査読有り 本文へのリンクあり 国際誌
2018年5月1日

Pancreatic tumor microenvironment confers highly malignant properties on pancreatic cancer cells

Oncogene
  • Kei Takahashi
  • ,
  • Shogo Ehata
  • ,
  • Daizo Koinuma
  • ,
  • Yasuyuki Morishita
  • ,
  • Manabu Soda
  • ,
  • Hiroyuki Mano
  • ,
  • Kohei Miyazono

37
21
開始ページ
2757
終了ページ
2772
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/s41388-018-0144-0

Tumor microenvironment plays a pivotal role in cancer progression; however, little is known regarding how differences in the microenvironment affect characteristics of cancer cells. Here, we investigated the effects of tumor microenvironment on cancer cells by using mouse tumor models. After three cycles of inoculation and extraction of human pancreatic cancer cells, including SUIT-2 and Panc-1 cells, from tumors, distinct cancer cell lines were established: 3P cells from the pancreas obtained using the orthotopic tumor model and 3sc cells from subcutaneous tissue obtained using the subcutaneous tumor model. On re-inoculation of these cells, the 3sc cells and, more prominently, the 3P cells, exhibited higher tumorigenic activity than the parental cells. The 3P cells specifically exhibited low E-cadherin expression and high invasiveness, suggesting that they were endowed with the highest malignant characteristics. RNA-sequence analysis demonstrated that distinct signaling pathways were activated in each cell line and that the 3P cells acquired a cancer stem cell-like phenotype. Among cancer stem cell-related genes, those specifically expressed in the 3P cells, including NES, may be potential new targets for cancer therapy. The mechanisms underlying the development of highly malignant cancer cell lines were investigated. Individual cell clones within the parental cells varied in tumor-forming ability, indicating the presence of cellular heterogeneity. Moreover, the tumor-forming ability and the gene expression profile of each cell clone were altered after serial orthotopic inoculations. The present study thus suggests that both selection and education processes by tumor microenvironment are involved in the development of highly malignant cancer cells.

リンク情報
DOI
https://doi.org/10.1038/s41388-018-0144-0
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/29511349
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5966364
Scopus
https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85042863352&origin=inward 本文へのリンクあり
Scopus Citedby
https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85042863352&origin=inward
ID情報
  • DOI : 10.1038/s41388-018-0144-0
  • ISSN : 0950-9232
  • eISSN : 1476-5594
  • PubMed ID : 29511349
  • PubMed Central 記事ID : PMC5966364
  • SCOPUS ID : 85042863352

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