TY  - JOUR
A1  - Boschert, Verena
A1  - Klenk, Nicola
A1  - Abt, Alexander
A1  - Raman, Sudha Janaki
A1  - Fischer, Markus
A1  - Brands, Roman C.
A1  - Seher, Axel
A1  - Linz, Christian
A1  - Müller-Richter, Urs D. A.
A1  - Bischler, Thorsten
A1  - Hartmann, Stefan
T1  - The influence of Met receptor level on HGF-induced glycolytic reprogramming in head and neck squamous cell carcinoma
JF  - International Journal of Molecular Sciences
N2  - Head and neck squamous cell carcinoma (HNSCC) is known to overexpress a variety of receptor tyrosine kinases, such as the HGF receptor Met. Like other malignancies, HNSCC involves a mutual interaction between the tumor cells and surrounding tissues and cells. We hypothesized that activation of HGF/Met signaling in HNSCC influences glucose metabolism and therefore substantially changes the tumor microenvironment. To determine the effect of HGF, we submitted three established HNSCC cell lines to mRNA sequencing. Dynamic changes in glucose metabolism were measured in real time by an extracellular flux analyzer. As expected, the cell lines exhibited different levels of Met and responded differently to HGF stimulation. As confirmed by mRNA sequencing, the level of Met expression was associated with the number of upregulated HGF-dependent genes. Overall, Met stimulation by HGF leads to increased glycolysis, presumably mediated by higher expression of three key enzymes of glycolysis. These effects appear to be stronger in Met\(^{high}\)-expressing HNSCC cells. Collectively, our data support the hypothesized role of HGF/Met signaling in metabolic reprogramming of HNSCC.
KW  - HNSCC
KW  - head and neck cancer
KW  - HGF
KW  - Met
KW  - cancer metabolism
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235995
SN  - 1422-0067
VL  - 21
IS  - 2
ER  - 
TY  - JOUR
A1  - Boschert, Verena
A1  - Teusch, Jonas
A1  - Aljasem, Anwar
A1  - Schmucker, Philipp
A1  - Klenk, Nicola
A1  - Straub, Anton
A1  - Bittrich, Max
A1  - Seher, Axel
A1  - Linz, Christian
A1  - Müller-Richter, Urs D. A.
A1  - Hartmann, Stefan
T1  - HGF-induced PD-L1 expression in head and neck cancer: preclinical and clinical findings
JF  - International Journal of Molecular Sciences
N2  - Head and neck squamous cell carcinoma (HNSCC) is a widespread disease with a low survival rate and a high risk of recurrence. Nowadays, immune checkpoint inhibitor (ICI) treatment is approved for HNSCC as a first-line treatment in recurrent and metastatic disease. ICI treatment yields a clear survival benefit, but overall response rates are still unsatisfactory. As shown in different cancer models, hepatocyte growth factor/mesenchymal–epithelial transition (HGF/Met) signaling contributes to an immunosuppressive microenvironment. Therefore, we investigated the relationship between HGF and programmed cell death protein 1 (PD-L1) expression in HNSCC cell lines. The preclinical data show a robust PD-L1 induction upon HGF stimulation. Further analysis revealed that the HGF-mediated upregulation of PD-L1 is MAP kinase-dependent. We then hypothesized that serum levels of HGF and soluble programmed cell death protein 1 (sPD-L1) could be potential markers of ICI treatment failure. Thus, we determined serum levels of these proteins in 20 HNSCC patients before ICI treatment and correlated them with treatment outcomes. Importantly, the clinical data showed a positive correlation of both serum proteins (HGF and sPD-L1) in HNSCC patient’s sera. Moreover, the serum concentration of sPD-L1 was significantly higher in ICI non-responsive patients. Our findings indicate a potential role for sPD-L1 as a prognostic marker for ICI treatment in HNSCC.
KW  - HNSCC
KW  - head and neck cancer
KW  - HGF
KW  - Met
KW  - PD-L1
KW  - immune therapy
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236220
SN  - 1422-0067
VL  - 21
IS  - 20
ER  -