Establishment of head and neck squamous cell carcinoma mouse models for cetuximab resistance and sensitivity  

作　　者：Hannah Zaryouh Ines De Pauw Hasan Baysal Joran Melis Valentin Van den Bossche Christophe Hermans Ho Wa Lau Hide Lambrechts Celine Merlin Cyril Corbet Marc Peeters Jan Baptist Vermorken Jorrit De Waele Filip Lardon An Wouters 

机构地区：[1]Center for Oncological Research(CORE),Integrated Personalized&Precision Oncology Network(IPPON),University of Antwerp,Campus Drie Eiken,Antwerp 2610,Belgium [2]Pole of Pharmacology and Therapeutics(FATH),Institut de Recherche Experimentale et Clinique(IREC),UCLouvain,Brussels B-1200,Belgium [3]institut Roi Albert Il,Department of Medical Oncology,Cliniques Universitaires Saint-Luc,Brussels B-1200,Belgium [4]Department of Medical Oncology,Antwerp University Hospital,Edegem 2650,Belgium

出　　处：《Cancer Drug Resistance》2023年第4期709-728,共20页癌症耐药（英文）

基　　金：funded by“Kom op tegen Kanker”(Stand up to Cancer),the Flemish Cancer Society(grant number:34986).

摘　　要：Aim:Acquired resistance to the targeted agent cetuximab poses a significant challenge in finding effective anti-cancer treatments for head and neck squamous cell carcinoma(HNSCC).To accurately study novel combination treatments,suitable preclinical mouse models for cetuximab resistance are key yet currently limited.This study aimed to optimize an acquired cetuximab-resistant mouse model,with preservation of the innate immunity,ensuring intact antibody-dependent cellular cytotoxicity(ADCC)functionality.Methods:Cetuximab-sensitive and acquired-resistant HNSCC cell lines,generated in vitro,were subcutaneously engrafted in Rag2 knock-out(KO),BALB/c Nude and CB17 Scid mice with/without Matrigel or Geltrex.Once tumor growth was established,mice were intraperitoneally injected twice a week with cetuximab for a maximum of 3 weeks.In addition,immunohistochemistry was used to evaluate the tumor and its microenvironment.Results:Despite several adjustments in cell number,cell lines and the addition of Matrigel,Rag2 KO and BALB/C Nude mice proved to be unsuitable for xenografting our HNSCC cell lines.Durable tumor growth of resistant SC263-R cells could be induced in CB17 Scid mice.However,these cells had lost their resistance phenotype in vivo.Immunohistochemistry revealed a high infiltration of macrophages in cetuximab-treated SC263-R tumors.FaDu-S and FaDu-R cells successfully engrafted into CB17 Scid mice and maintained their sensitivity/resistance to cetuximab.Conclusion:We have established in vivo HNSCC mouse models with intact ADCC functionality for cetuximab resistance and sensitivity using the FaDu-R and FaDu-S cell lines,respectively.These models serve as valuable tools for investigating cetuximab resistance mechanisms and exploring novel drug combination strategies.

关 键 词：HNSCC cetuximab resistance xenograft mouse model immunodeficient mice 

分 类 号：R739.91[医药卫生—肿瘤]