Open AccessADAM 23 is downregulated in side population and suppresses lung metastasis of lung carcinoma cells
Author(s) -
Ota Masahide,
Mochizuki Satsuki,
Shimoda Masayuki,
Abe Hitoshi,
Miyamae Yuka,
Ishii Ken,
Kimura Hiroshi,
Okada Yasunori
Publication year - 2016
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12895
Subject(s) - side population , gene knockdown , population , cancer research , lung cancer , biology , a549 cell , metastasis , cell sorting , cancer stem cell , cancer cell , microbiology and biotechnology , cell culture , immunology , cancer , stem cell , pathology , medicine , flow cytometry , genetics , environmental health
Cancer cells contain a small population of cancer stem cells or cancer initiating cells, which can be enriched in the side population ( SP ) after fluorescence activated cell sorting. To examine the members of the ADAM , ADAMTS and MMP gene families related to phenotypes of the SP and the main population ( MP ), we screened the expression of all the members in the propagated SP and MP of A549 lung adenocarcinoma cells, and found that the relative expression ratio of ADAM 23 in the MP to the SP is most highly increased, but none of them are increased in the SP . A similar result on the ADAM 23 expression was obtained with another cell line, Calu‐3 cells. Overexpression of ADAM 23 inhibited colony formation, cell adhesion and migration, and knockdown of ADAM 23 by sh RNA showed the reverse effects. ADAM 23‐mediated suppression of colony formation, cell adhesion and migration was greatly reduced by treatment with neutralizing anti‐ ADAM 23 antibody, anti‐αvβ3 integrin antibody and/or ADAM 23 disintegrin peptide. Expression of cancer stem cell‐related genes, including AKRC 1/2, TM 4 SF 1 and NR 0B1, was increased by knockdown of ADAM 23. In addition, lung metastasis of A549 transfectants with different levels of ADAM 23 expression was negatively regulated by the ADAM 23 expression levels. Our data provide evidence that ADAM 23 plays a role in suppression of cancer cell progression through interaction with αvβ3 integrin, and suggest that downregulation of ADAM 23 in SP cells may contribute toward providing a cancer stem cell phenotype by facilitating the activity of integrin αvβ3.