39 - Freie Mitteilung
Clinical works I
16. Mai 2019, 08:30 - 10:00, Bellavista 2, 6. OG
The co-expression of CD26 and TGF-β1 renders lung cancer targetable to CD26-inhibition
N. Enz1, F. Janker2, S. Andreoli2, C. Opelz2, W. Weder2, J. H. Jang2, W. Jungraithmayr1, Presenter: W. Jungraithmayr1 (1Rostock/DE, 2Zurich)
CD26/dipeptidyl peptidase 4 (CD26) is a transmembrane multifunctional molecule present on various haematopoetic and somatic cells. We showed previously that lung cancer growth is decreased upon CD26-inhibition. Also, we could demonstrate that CD26 is highly expressed in human lung adenocarcinoma. We here extended our analysis on the expression of CD26 within the lung tumor microenvironment.
Samples from patients with lung malignancies (n=103) including adenocarcinoma (n=38), squamous carcinoma (n=26), lung metastases (n=14), and others (n=25) were analyzed against normal lung on a gene level for CD26, TGF-β1, TGF-R1, TGF-R2 and CCL2 by RT-qPCR, on a protein level for CD26 and TGF-β1 by ELISA, and by immunohistochemistry (IHC) for CD26 (n=80). The expression of CD26 on tumor cells was graded from 0 to 3.
Adenocarcinoma expressed significantly more CD26 than other thoracic malignancies (n=80, p=0.0001). While stage IA adenocarcinoma expresses significantly higher amounts of CD26 compared to stage IIIA (p=0.0019), levels of CD26 raised in stage IIIB and IV, however, without significance. Furthermore, we found a significant correlation between the gene expression of CD26 on tumors for TGF-β1 (p<0.0001), TGF-R1 (p=0.0004), and TGF-R2 (p<0.0001). Also, the pro-inflammatory chemokine ligand CCL2 was significantly correlated with CD26 (p=0.0011). The co-expression of CD26 and TGF-β1 could be additionally confirmed on a protein level.
We could confirm that CD26 is highly expressed in lung adenocarcinomas and that CD26 is co-expressed with pro-fibrotic proteins relevant to tumor microenvironment formation. This co-expression supports the potential for the treatment of lung cancer with CD26-inhibitors.