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sCADM1 as a new diagnostic marker of ATLL
and metastasis 1 (TIAM1), and induces signaling to actin fil- aments, leading to cell structure remodeling.42 sCADM1 may activate this TIAM1-actin signaling to modulate cellu- lar functions. It has also been reported that CADM1 expres- sion on tumor cells enhances the cytotoxic activities of cytotoxic T cells or natural killer cells via an interaction with Class I MHC-restricted T-cell-associated molecule (CRTAM).40,43 The CRTAM-CADM1 interaction acts as a costimulator of T-cell receptor (TCR) signaling that may help to eliminate tumor cells. Because sCADM1 has been reported to bind to the extracellular domain of CADM1 on the cell surface and inhibit CADM1 homophilic interac- tions,27 it is possible that sCADM1 may modulate immune responses under certain conditions. Future studies of the biological role of sCADM1 in anti-tumor immune respons- es will be important to obtain a better understanding of the molecular mechanisms of the immunological abnormalities in ATLL.44
To date, there has been no report identifying sCADM1 in cancers; however, it has been reported that CADM1 shedding was elevated in the lung epithelial cells of patients with idiopathic interstitial pneumonias45 or pul- monary emphysema,46 as well as in the pancreatic islets of patients with type 2 diabetes mellitus,47 which was accompanied by a decrease in full-length CADM1 levels and may be associated with the disruption of cell polarity and cell apoptosis.45,46 In ATLL, plasma sCADM1 levels drastically increased from chronic to acute-type ATLL with no apparent reduction in the expression of full-length CADM1, suggesting that sCADM1 may play a role in the malignant progression of ATLL.
In summary, sCADM1 is a promising biomarker not
only for monitoring the leukemic burden of ATLL patients, but also for predicting disease status. Thus, sCADM1 measurement may be valuable for the diagnosis of ATLL.
Disclosures
No conflicts of interests to disclose.
Contributions
SN performed research, analyzed data and wrote the manu- script; CS, AN, KSa, MY, IN, and MS performed research and analyzed data; TK, KSh, YK, TH, AK, ST, NN, MI, YS, KMo, MA, KMa, ES, AO, KSh, and TW provided clinical information and samples. YU, TM, and AI provided critical reagents; AU provided clinical information and samples, and critical evaluation of the manuscript; and KM conceived and designed the study, directed and supervised the research, and wrote the manuscript.
Acknowledgments
The authors are grateful to Dr. Hidekatsu Iha (Oita University, Japan), Dr. Yasuaki Yamada (Nagasaki University, Japan), and Dr. Naomichi Arima (Kagoshima University, Japan) for providing cell lines.
Funding
This work was supported in part by Grant-in-Aid for Scientific Research (B) (25293081 and 17H03581) (KM) from the Japanese Society for the Promotion of Science (JSPS), by the Platform of Supporting Cohort Study and Biospecimen Analysis, Grant-in-Aid for Scientific Research on Innovative Areas (16H06277) (TW), and by the Takeda Science Foundation (KM).
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