Abstract
In present study, we are to clear demonstrate the genetic evidence of IDO signaling's impact on invasion and metastasis in lung cancer. Here we examined IDO1 expression levels in non-small cell lung cancer (NSCLC) patients (64) tumor/normal pairs underwent RT-PCR and comprehensive histological, immunohistochemica and clinical analysis. The NSCLC cells stably expressing IDO1 was analyzed for migration and invasion assays and the regulatory mechanism in vitro and metastasis assays in vivo. As results, we reported that IDO1 expression increased by more than 3.2-fold in lung cancer compared with their corresponding non-tumor tissues, and the up-regulation of IDO1 is significantly correlated to TNM stage and lymph node-metastasis. The over-expression of IDO1 significantly encouraged the metastasis and invasion of lung cancer cells, and IDO1 could promote metastasis formation in vivo. Furthermore, we further found that p53 could attenuate IDO signaling in lung cancer cell migration partly. In conclusion, these results demonstrate that the IDO signaling's impact on invasion and metastasis and the suppressive effect of p53 on IDO1 in lung cancer, present one novel therapeutic strategy for early metastatic lung cancer in clinical.
Highlights
Distant metastasis and invasion are in charge of most cancer related deaths [1]
We reported that IDO1 expression increased by more than 3.2-fold in lung cancer compared with their corresponding non-tumor tissues, and the upregulation of IDO1 is significantly correlated to TNM stage and lymph node-metastasis
We further found that p53 could attenuate IDO signaling in lung cancer cell migration partly
Summary
Distant metastasis and invasion are in charge of most cancer related deaths [1]. The course of tumor metastasis compose of consequent steps including cancer cells invade into surrounding tissue, exist in circulation, stay at distant organs, and grow into tumor in the distant sites [2]. IDO-1 exerts a potent immunosuppressive effect through inhibiting T-lymphocytes and other immune cells. IDO-1 has been shown to induce immunosuppressive effects and favor tumor progression in animal models of lung cancer [4, 5]. Blockade of IDO-1 using small molecule inhibitors in combination with immune checkpoint blockade induces prominent antitumor responses in mouse models and reversal of tumor-associated immunosuppression by 1methyl-D-tryptophan appears to be dependent on host IDO1 expression [6]. We further found that IDO pathway is involved in NSCLC cell migration and invasion and p53 could negatively modulate IDO signaling partly. These results present a therapeutic strategy for early metastatic lung cancer
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
