Τίτλος:
Generation of non‐small cell lung cancer patient‐derived xenografts to study intratumor heterogeneity
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Recent advances in sequencing technologies have allowed the in‐depth molecular study of tumors, even at the single cell level. Sequencing efforts have uncovered a previously unappreci-ated heterogeneity among tumor cells, which has been postulated to be the driving force of tumor evolution and to facilitate recurrence, metastasis, and drug resistance. In the current study, focused on early‐stage operable non‐small cell lung cancer, we used tumor growth in patient‐derived xeno-graft (PDX) models in mice as a fast‐forward tumor evolution process to investigate the molecular characteristics of tumor cells that grow in mice, as well as the parameters that affect the grafting efficiency. We found that squamous cell carcinomas grafted significantly more efficiently compared with adenocarcinomas. Advanced stage, patient age and primary tumor size were positively correlated with grafting. Additionally, we isolated and characterized circulating tumor cells (CTC) from patients’ peripheral blood and found that the presence of CTCs expressing epithelial‐to‐mesenchy-mal (EMT) markers correlated with the grafting potential. Interestingly, exome sequencing of the PDX tumor identified genetic alterations in DNA repair and genome integrity genes that were un-der‐represented in the human primary counterpart. In conclusion, through the generation of a PDX biobank of NSCLC, we identified the clinical and molecular properties of tumors that affected growth in mice. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Συγγραφείς:
Kanaki, Z.
Voutsina, A.
Markou, A.
Pateras, I.S.
Potaris, K.
Avgeris, M.
Makrythanasis, P.
Athanasiadis, E.I.
Vamvakaris, I.
Patsea, E.
Vachlas, K.
Lianidou, E.
Georgoulias, V.
Kotsakis, A.
Klinakis, A.
Λέξεις-κλειδιά:
adult; age; aged; animal cell; animal experiment; animal model; animal tissue; Article; blood; cancer patient; cancer staging; circulating tumor cell; controlled study; disease classification; DNA repair; epithelial mesenchymal transition; human; human cell; human tissue; lung adenocarcinoma; lung non-small cell carcinoma cell line; major clinical study; mouse; non small cell lung cancer; nonhuman; squamous cell carcinoma; treatment outcome; tumor cell; tumor growth; tumor volume; whole exome sequencing
DOI:
10.3390/cancers13102446
