Periostin is a negative prognostic factor and promotes cancer cell proliferation in non-small cell lung cancer
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Toshimasa Okazaki1,3,6, Keiichi Tamai1, Rie Shibuya1, Mao Nakamura2, Mai Mochizuki1, Kazunori Yamaguchi2, Jiro Abe3, Satomi Takahashi3, Ikuro Sato4, Akira Kudo5, Yoshinori Okada6 and Kennichi Satoh1
1Division of Cancer Stem Cell, Miyagi Cancer Center Research Institute, Natori, Japan
2Division of Molecular and Cellular Oncology, Miyagi Cancer Center Research Institute, Natori, Japan
3Department of Thoracic Surgery, Miyagi Cancer Center, Natori, Japan
4Department of Pathology, Miyagi Cancer Center, Natori, Japan
5Department of Biological Information, Tokyo Institute of Technology, Yokohama, Japan
6Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan
Keiichi Tamai, email: [email protected]
Keywords: periostin; lung cancer; cell proliferation; prognostic factor; prognosis
Received: December 12, 2017 Accepted: April 28, 2018 Published: July 27, 2018
Periostin is a matricellular protein that is secreted by fibroblasts and interacts with various cell-surface integrin molecules. Although periostin is known to support tumor development in human malignancies, little is known about its effect on lung-cancer progression. We here demonstrate that periostin is a negative prognostic factor that increases tumor proliferation through ERK signaling in non-small cell lung carcinoma. We classified 189 clinical specimens from patients with non-small cell lung-cancer according to high or low periostin expression, and found a better prognosis for patients with low rather than high periostin, even in cases of advanced-stage cancer. In a syngenic implantation model, murine Ex3LL lung-cancer cells formed smaller tumor nodules in periostin−/− mice than in periostin+/+ mice, both at the primary site and at metastatic lung sites. An in vitro proliferation assay showed that stimulation with recombinant periostin increased Ex3LL-cell proliferation. We also found that periostin promotes ERK phosphorylation, but not Akt or FAK activation. These findings suggest that periostin represents a potential target in lung-cancer tumor progression.
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