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J Cancer Metastasis Treat 2016;2 Suppl 1

chemokine (SDF-1), which is involved in adhesion Jürgen Debus 6,15 , Claus Belka 7,16 , Steffi Pigorsch 7,17 ,
and migration of cancer stem cells. Additionally, Stephanie E. Combs 7,17 , David Mönnich 8,18 , Daniel Zips 8,18 ,
cathepsin X cleaves C-terminal ends of enolase and Gustavo B. Baretton 1,21 , Frank Buchholz 1,22 , Michael
1,9
profilin, another two proteins that were suggested to Baumann , Mechthild Krause 1,9
alter cancer stem cells adhesion, migration and their 1 German Cancer Research Center (DKFZ), Heidelberg and German
metastatic potential. Cathepsin X also cleaves beta-2 Cancer Consortium (DKTK) partner site: Dresden, Germany;
chain in Mac-1 and LFA-1 integrin receptors and binds 2 German Cancer Research Center (DKFZ), Heidelberg and German
to alpha-v-beta 5 integrin receptor via RGD motif in Cancer Consortium (DKTK) partner site: Berlin, Germany;
German Cancer Research Center (DKFZ), Heidelberg and German
3
the pro-region, affecting in this way the adhesion of Cancer Consortium (DKTK) partner site: Essen, Germany;
endothelial and tumor cells and presumably cancer 4 German Cancer Research Center (DKFZ), Heidelberg and German
stem cells. Cathepsin X knock out accelerates a Cancer Consortium (DKTK) partner site: Frankfurt, Germany;
German Cancer Research Center (DKFZ), Heidelberg and German
5
progress to senescence in vitro and in vivo via p16, Cancer Consortium (DKTK) partner site: Freiburg, Germany;
p21 and p53 signaling pathway. 6 German Cancer Research Center (DKFZ), Heidelberg and German
Cancer Consortium (DKTK) partner site: Heidelberg, Germany;
7 German Cancer Research Center (DKFZ), Heidelberg and German
The activity of cysteine cathepsins is regulated by Cancer Consortium (DKTK) partner site: Munich, Germany;
endogenous protein inhibitors cystatins. Of these, 8 German Cancer Research Center (DKFZ), Heidelberg and German
cystatin F is the only cystatin that is localized in Cancer Consortium (DKTK) partner site: Tübingen, Germany;
Universitätsklinikum Carl Gustav Carus der TU Dresden, Dresden, Germany;
9
endosomal/lysosomal vesicles. In cytotoxic T cells and 10 OncoRay - National Center for Radiation Research in Oncology, Faculty of
NK cells its main role is the control of progranzyme Medicine and University Hospital Carl Gustav Carus, Technische Universität
convertase activity of cathepsins C and H and Dresden, Dresden, Germany;
Department of Radiooncology and Radiotherapy, Charité University Hospital,
11
consequently, the granzyme dependent cytotoxic Berlin, Germany;
function. It is known that cytotoxic function of NK 12 Department of Radiotherapy, Medical Faculty, University of Duisburg-Essen,
cells is suppressed after their interaction with tumor Essen, Germany;
Department of Radiotherapy and Oncology, Goethe-University Frankfurt,
13
cells or cancer stem cells, the status is termed split Frankfurt, Germany;
anergy. The mechanism includes cytokine cross-talk, 14 Department of Radiation Oncology, University of Freiburg, Freiburg, Germany;
Heidelberg Institute of Radiation Oncology (HIRO), National Center for
however, target cells may also secrete inactive dimeric 15 Radiation Research in Oncology (NCRO), University of Heidelberg Medical
cystatin F which after internalization to NK cells enters School and German Cancer Research Center (DKFZ), Heidelberg, Germany;
endosomal/lysosomal vesicles and after activation/ 16 Department of Radiotherapy and Radiation Oncology, Ludwig-Maximilians-
monomerisation inhibits cathepsins C and H and Universität, Munich, Germany;
Department of Radiation Oncology, Technische Universität München,
17
down-regulates cell cytotoxicity. Anergized NK cells Munich, Germany;
cause differentiation of cancer stem cells by secreted 18 Department of Radiation Oncology, Faculty of Medicine and University
cytokines and as a result, differentiated tumors become Hospital Tübingen, Eberhard Karls Universität Tübingen, Tübingen, Germany;
19
Department of Otorhinolaryngology, Faculty of Medicine and University Hospital
resistant to NK cell-mediated cytotoxicity. Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany;
20 Department of Oral and Maxillofacial Surgery, Faculty of Medicine and
Our results show that some of cysteine cathepsins University Hospital Carl Gustav Carus, Technische Universität Dresden,
Dresden, Germany;
and their endogenous inhibitors have specific roles 21 Institute of Pathology, Faculty of Medicine and University Hospital Carl
in cancer stem cell functions designating them as Gustav Carus, Technische Universität Dresden, Dresden, Germany;
University Cancer Center (UCC), Medical Systems Biology, University Hospital
potential therapeutic targets for improving anticancer 22 Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
therapy.
Aim: The outcome after curative treatment of locally
Key words: advanced head and neck squamous cell carcinoma
Cathepsin, cystatin, anergy, SDF-1, profilin, enolase (LA-HNSCC) remains unsatisfactory. Except of
A8 HPV-infection status there is no further established
biomarker for treatment stratification. Currently,
Hypoxia and expression levels of cancer treatment decisions are mainly based on the tumor site
stem cell markers are prognostic for loco- and the TNM system regardless of the heterogeneous
regional control after radiochemotherapy in biology of HNSCC. For identification and validation of
locally advanced head and neck squamous biomarkers, the German Cancer Consortium Radiation
cell carcinoma Oncology Group (DKTK-ROG) initiated a multicenter
retrospective/prospective biomarker trial to explore their

Fabian Lohaus , Annett Linge 1,10 , Steffen Löck , Volker impact on locoregional control (LRC) after postoperative
1,9
10
Gudziol , Alexander Nowak , Cläre von Neubeck 1,10 , (PORT-C) and primary radiochemotherapy. Methods:
20
19
Inge Tinhofer 2,11 , Volker Budach 2,11 , Ali Sak 3,12 , Martin In the multicenter retrospective part of the study,
Stuschke 3,12 , Panagiotis Balermpas 4,13 , Claus Rödel 4,13 , 355 patients with HNSCC of the oral cavity, oro- and
Melanie Avlar 5,14 , Anca-Ligia Grosu 5,14 , Amir Abdollahi 6,15 , hypopharynx were included. All patients received
Journal of Cancer Metastasis and Treatment ¦ Volume 2 ¦ November 16, 2016 421