Rebecca Kesselring1, Annette Thiel2, Ralph Pries3, Stefan Fichtner-Feigl4, Stefan Brunner4, Philipp Seidel3, Karl-Ludwig Bruchhage3, Barbara Wollenberg5. 1. Department of Otorhinolaryngology and Plastic Surgery, University of Luebeck, Ratzeburger Allee 160, 23562 Luebeck, Germany; Department of Surgery, University Medical Center Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany. 2. Department of Otorhinolaryngology and Plastic Surgery, University of Luebeck, Ratzeburger Allee 160, 23562 Luebeck, Germany; Department of Internal Medicine, University Medical Center Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany. 3. Department of Otorhinolaryngology and Plastic Surgery, University of Luebeck, Ratzeburger Allee 160, 23562 Luebeck, Germany. 4. Department of Surgery, University Medical Center Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany. 5. Department of Otorhinolaryngology and Plastic Surgery, University of Luebeck, Ratzeburger Allee 160, 23562 Luebeck, Germany. Electronic address: Barbara.wollenberg@uksh.de.
Abstract
BACKGROUND: Membrane-bound complement restriction proteins (mCRPs) CD46, CD55 and CD59 enable tumour cells to evade complement dependent cytotoxicity and antibody-dependent killing mechanisms. But less is known about the role of these mCRPs in head and neck cancer. METHODS: In this study we determined the expression of the mCRPs on head and neck squamous cell carcinoma (HNSCC) cell lines, on tumour tissue and TDLNs (tumour-draining lymph nodes) as well as on lymphocytes from HNSCC patients. The influence of the HNSCC microenvironment on the mCRP regulation was analysed using Flow Cytometry, Western blotting and small interfering RNAs (siRNA) transfection studies. RESULTS: We examined the effects of the HNSCC tumour milieu on the expression levels of CD46, CD55 and CD59. We investigated the susceptibility of HNSCC cells to CDC (complement-dependent cytotoxicity) while silencing the mCRPs. Our results demonstrate a huge influence of the HNSCC tumour microenvironment on the regulation of mCRP expression and show a reciprocal regulation between the different mCRPs themselves. CONCLUSIONS: In summary, our data indicate that HNSCC has evolved different strategies to evade complement attacks and that the tumour microenvironment leads to the enhancement of complement resistance of the surrounding tissue.
BACKGROUND: Membrane-bound complement restriction proteins (mCRPs) CD46, CD55 and CD59 enable tumour cells to evade complement dependent cytotoxicity and antibody-dependent killing mechanisms. But less is known about the role of these mCRPs in head and neck cancer. METHODS: In this study we determined the expression of the mCRPs on head and neck squamous cell carcinoma (HNSCC) cell lines, on tumour tissue and TDLNs (tumour-draining lymph nodes) as well as on lymphocytes from HNSCC patients. The influence of the HNSCC microenvironment on the mCRP regulation was analysed using Flow Cytometry, Western blotting and small interfering RNAs (siRNA) transfection studies. RESULTS: We examined the effects of the HNSCC tumour milieu on the expression levels of CD46, CD55 and CD59. We investigated the susceptibility of HNSCC cells to CDC (complement-dependent cytotoxicity) while silencing the mCRPs. Our results demonstrate a huge influence of the HNSCC tumour microenvironment on the regulation of mCRP expression and show a reciprocal regulation between the different mCRPs themselves. CONCLUSIONS: In summary, our data indicate that HNSCC has evolved different strategies to evade complement attacks and that the tumour microenvironment leads to the enhancement of complement resistance of the surrounding tissue.
Authors: Anne Lok; Geraldine Descamps; Benoit Tessoulin; David Chiron; Marion Eveillard; Catherine Godon; Yannick Le Bris; Astrid Vabret; Celine Bellanger; Laurent Maillet; Sophie Barillé-Nion; Marc Gregoire; Jean-François Fonteneau; Steven Le Gouill; Philippe Moreau; Frederic Tangy; Martine Amiot; Agnes Moreau-Aubry; Catherine Pellat-Deceunynck Journal: Blood Adv Date: 2018-12-11
Authors: John J Wallbillich; Paul Mh Tran; Shan Bai; Lynn Kh Tran; Ashok K Sharma; Sharad A Ghamande; Jin-Xiong She Journal: Am J Cancer Res Date: 2020-05-01 Impact factor: 6.166
Authors: Brittany Montesino; Agata Steenackers; Juan M Lozano; Geoffrey D Young; Nan Hu; Robert Sackstein; Kevin Brown Chandler Journal: Glycobiology Date: 2022-04-21 Impact factor: 4.313
Authors: Anne Monks; Yingdong Zhao; Curtis Hose; Hossein Hamed; Julia Krushkal; Jianwen Fang; Dmitriy Sonkin; Alida Palmisano; Eric C Polley; Laura K Fogli; Mariam M Konaté; Sarah B Miller; Melanie A Simpson; Andrea Regier Voth; Ming-Chung Li; Erik Harris; Xiaolin Wu; John W Connelly; Annamaria Rapisarda; Beverly A Teicher; Richard Simon; James H Doroshow Journal: Cancer Res Date: 2018-10-24 Impact factor: 12.701
Authors: F Cimmino; M Avitabile; L Pezone; G Scalia; D Montanaro; M Andreozzi; L Terracciano; A Iolascon; M Capasso Journal: Oncogenesis Date: 2016-04-04 Impact factor: 7.485