Increased Tumor Growth Rate and Mesenchymal Properties of NSCLC-Patient-Derived Xenograft Models during Serial Transplantation

Abstract

Non-small-cell lung cancer (NSCLC) is the leading cause of cancer death worldwide. The high mortality is very often a consequence of its late diagnosis when the cancer is already locally advanced or has disseminated. Advances in the study of NSCLC tumors have been achieved by using in vivo models, such as patient-derived xenografts. Apart from drug screening, this approach may also be useful for study of the biology of the tumors. In the present study, surgically resected primary lung cancer samples (n = 33) were implanted in immunodeficient mice, and nine were engrafted successfully, including seven adenocarcinomas, one squamous-cell carcinoma, and one large-cell carcinoma. ADC tumors bearing the KRAS-G12C mutation were the most frequently engrafted in our PDX collection. Protein expression of vimentin, ezrin, and Ki67 were evaluated in NSCLC primary tumors and during serial transplantation by immunohistochemistry, using H-score. Our data indicated a more suitable environment for solid adenocarcinoma, compared to other lung tumor subtypes, to grow and preserve its architecture in mice, and a correlation between higher vimentin and ezrin expression in solid adenocarcinomas. A correlation between high vimentin expression and lung adenocarcinoma tumors bearing KRAS-G12C mutation was also observed. In addition, tumor evolution towards more proliferative and mesenchymal phenotypes was already observed in early PDX tumor passages. These PDX models provide a valuable platform for biomarker discovery and drug screening against tumor growth and EMT for lung cancer translational research.

PD-L1-Mediated Immunosuppression in Oral Squamous Cell Carcinoma: Relationship With Macrophage Infiltration and Epithelial to Mesenchymal Transition Markers

“…EMT is a novel mechanism involved in cancer metastasis, by which epithelial cells acquire both mesenchymal and epithelial phenotypes for cell migration and proliferation. The type III intermediate filament protein VIM that constitutes a key cytoskeletal element of mesenchymal cells, is a canonical marker of EMT process, and EMT process is characterized by marked VIM upregulation ( 47 , 48 ). It is generally accepted that epithelial cells undergoing EMT are able to survive better under adverse environmental conditions, which enables tumor cells to evade immune destruction ( 49 , 50 ).…”

Knowledge, attitude, and practice of lung cancer screening and associated factors among high-risk population in Lanzhou, China: A cross-sectional study

“…[3] A higher survival rate is strongly associated with lung cancer diagnosis at the earliest stage, but only 16% of lung cancer cases are diagnosed at an early-stage. [4] Low-dose computed tomography (LDCT) has been proven to be an effective method for lung cancer screening and can potentially reduce mortality from lung cancer by 20.0% among high-risk individuals. [5] Currently, screening for lung cancer with LDCT in high-risk populations is recommended according to the National Comprehensive Cancer Network, [6] Clinical Practice Guideline, and China guidelines for the screening and early detection of lung cancer.…”

Caregiver burden for informal caregivers of patients after surgical treatment of early‐stage lung cancer

“…Lung cancer is a fatal disease that threatens human health and lives. In the early (occult) stage, lung cancer has no specific symptoms and manifestations, most of lung cancer cases were diagnosed at an advanced stage while <20% were diagnosed at an early stage (Pardo‐Sánchez et al, 2021). The number of individuals diagnosed with early‐stage lung cancer is anticipated to increase due to the wide use and application of high‐end low‐dose computed tomography (LDCT) scanning and enhancement of people's health consciousness.…”