Open AccessCD109 regulates in vivo tumor invasion in lung adenocarcinoma through TGF‐β signaling
Author(s) -
Taki Tetsuro,
Shiraki Yukihiro,
Enomoto Atsushi,
Weng Liang,
Chen Chen,
Asai Naoya,
Murakumo Yoshiki,
Yokoi Kohei,
Takahashi Masahide,
Mii Shinji
Publication year - 2020
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.14673
Subject(s) - stromal cell , adenocarcinoma , stroma , lung , cancer research , immunohistochemistry , lung cancer , biology , adenocarcinoma of the lung , in vivo , pathology , oncology , medicine , cancer , immunology , microbiology and biotechnology
Stromal invasion is considered an important prognostic factor in patients with lung adenocarcinoma. The mechanisms underlying the formation of tumor stroma and stromal invasion have been studied in the lung; however, they are still unclear. CD109 is a glycosylphosphatidylinositol‐anchored glycoprotein highly expressed in several types of human malignant tumors including lung cancers. In this study, we investigated the in vivo functions of CD109 protein in malignant lung tumors. Initially, we identified an association between higher expression of CD109 protein in human lung adenocarcinoma and a significantly worse prognosis, according to immunohistochemical analysis. We also showed that CD109 deficiency significantly reduced the area of stromal invasive lesions in a genetically engineered CD109‐deficient lung adenocarcinoma mouse model, which correlated with the results observed in human lung adenocarcinoma. Furthermore, we identified latent TGF‐β binding protein‐1 (LTBP1) as a CD109‐interacting protein using mass spectrometry and confirmed their interaction by co‐immunoprecipitation. Importantly, increased CD109 expression enhanced stromal TGF‐β activation in the presence of LTBP1. Therefore, these data suggest the significance of the regulation of TGF‐β signaling through CD109 and LTBP1 interaction in tumor stroma and also reveal the importance of CD109 expression levels in promoting lung cancer cell proliferation, migration, and invasion, and thus predicting the outcome of patients suffering from lung adenocarcinoma. Therefore, CD109 protein could be a potential therapeutic target for this disease.