cancer-associated fibroblasts; Notch signaling; head and neck cancer; local recurrence
Roh Vincent, Hiou‐Feige Agnès, Misetic Vinko, Rivals Jean‐Paul, Sponarova Jana, Teh Muy‐Teck, Ferreira Lopes Silvia, Truan Zinnia, Mermod Maxime, Monnier Yan, Hess Jochen, Tolstonog Genrich V, Simon Christian (2019), The transcription factor FOXM1 regulates the balance between proliferation and aberrant differentiation in head and neck squamous cell carcinoma, in The Journal of Pathology
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Bordignon Pino, Bottoni Giulia, Xu Xiaoying, Popescu Alma S., Truan Zinnia, Guenova Emmanuella, Kofler Lukas, Jafari Paris, Ostano Paola, Röcken Martin, Neel Victor, Dotto G. Paolo (2019), Dualism of FGF and TGF-β Signaling in Heterogeneous Cancer-Associated Fibroblast Activation with ETV1 as a Critical Determinant, in Cell Reports
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Roh Vincent, Abramowski Pierre, Hiou-Feige Agnès, Cornils Kerstin, Rivals Jean-Paul, Zougman Alexandre, Aranyossy Tim, Thielecke Lars, Truan Zinnia, Mermod Maxime, Monnier Yan, Prassolov Vladimir, Glauche Ingmar, Nowrouzi Ali, Abdollahi Amir, Fehse Boris, Simon Christian, Tolstonog Genrich V. (2018), Cellular Barcoding Identifies Clonal Substitution as a Hallmark of Local Recurrence in a Surgical Model of Head and Neck Squamous Cell Carcinoma, in Cell Reports
, 25(8), 2208-2222.e7.
Mermod Maxime, Hiou-Feige Agnès, Bovay Esther, Roh Vincent, Sponarova Jana, Bongiovanni Massimo, Vermeer Daniel W., Lee John H., Petrova Tatiana V., Rivals Jean-Paul, Monnier Yan, Tolstonog Genrich V., Simon Christian (2018), Mouse model of postsurgical primary tumor recurrence and regional lymph node metastasis progression in HPV-related head and neck cancerSurgical model of HPV-related head and neck cancer, in International Journal of Cancer
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Tolstonog Genrich, Simon Christian (2017), Trends in Surgical Research in Head and Neck Cancer, in Current treatment options in oncology
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Head and neck cancer (HNC) is one of the most commonly diagnosed cancers worldwide. Loco-regional control, particularly the control at the primary tumor site, is an important prognostic factor for survival and clinical evidence has emerged that such local control depends greatly on an invasive phenotype of the primary cancer. In the recent years it became clear that cancer-associated fibroblasts (CAFs) are intimately involved in HNC progression and that their density and localization predict the aggressiveness of the disease and potential failure in the loco-regional control. Hence, we hypothesized that invasion and thus local control of HNCs may be related to CAFs in the proximity of the HNCs. We plan to address the three following aims in this study: Firstly, based on a membrane-enriched proteomic analysis of CAFs and tumor cell lines, established from clinical samples, we plan to correlate selected CAF-associated proteins with clinico-pathological characteristics. Secondly, based on our initial findings of an expression of NOTCH2 and the receptor tyrosine kinase DDR2 on the CAFs, we aim to investigate the role of these two proteins in the tumor-supportive function of CAFs. Finally, we will use our recently established xenogeneic and syngeneic orthotopic mouse models that specifically reconstitute the biological behavior of human HNC and in vitro co-cultures of patient-derived CAFs with HNC cells to demonstrate an in vivo effect of the functional circuitries between CAFs and tumor cells on tumor recurrence after surgical resection. Altogether, we plan to explore if modulation of CAFs and their interaction with tumor cells will reduce cancer cell invasion and prevent post-surgical HNC recurrence.