論文

査読有り 国際誌
2019年12月

PODXL1 promotes metastasis of the pancreatic ductal adenocarcinoma by activating the C5aR/C5a axis from the tumor microenvironment.

Neoplasia (New York, N.Y.)
  • Ken Saito
  • ,
  • Hidekazu Iioka
  • ,
  • Satoshi Maruyama
  • ,
  • I Wayan Sumardika
  • ,
  • Masakiyo Sakaguchi
  • ,
  • Eisaku Kondo

21
12
開始ページ
1121
終了ページ
1132
記述言語
英語
掲載種別
DOI
10.1016/j.neo.2019.09.003

Pancreatic invasive ductal adenocarcinoma (PDAC) is a representative intractable malignancy under the current cancer therapies, and is considered a scirrhous carcinoma because it develops dense stroma. Both PODXL1, a member of CD34 family molecules, and C5aR, a critical cell motility inducer, have gained recent attention, as their expression was reported to correlate with poor prognosis for patients with diverse origins including PDAC; however, previous studies reported independently on their respective biological significance. Here we demonstrate that PODXL1 is essential for metastasis of PDAC cells through its specific interaction with C5aR. In vitro assay demonstrated that PODXL1 bound to C5aR, which stabilized C5aR protein and recruited it to cancer cell plasma membranes to receive C5a, an inflammatory chemoattractant factor. PODXL1 knockout in PDAC cells abrogated their metastatic property in vivo, emulating the liver metastatic mouse model treated with anti-C5a neutralizing antibody. In molecular studies, PODXL1 triggered EMT on PDAC cells in response to stimulation by C5a, corroborating PODXL1 involvement in PDAC cellular invasive properties via specific interaction with the C5aR/C5a axis. Confirming the molecular assays, histological examination showed coexpression of PODXL1 and C5aR at the invasive front of primary cancer nests as well as in liver metastatic foci of PDAC both in the mouse metastasis model and patient tissues. Hence, the novel direct interaction between PODXL1 and the C5aR/C5a axis may provide a better integrated understanding of PDAC biological characteristics including its tumor microenvironment factors.

リンク情報
DOI
https://doi.org/10.1016/j.neo.2019.09.003
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/31759250
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6872781
ID情報
  • DOI : 10.1016/j.neo.2019.09.003
  • PubMed ID : 31759250
  • PubMed Central 記事ID : PMC6872781

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