ArticleCell & bioscience2017
Hypoxic 3D in vitro culture models reveal distinct resistance processes to TKIs in renal cancer cells.
Article in Cell & bioscience, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 39 citations in OpenAlex.
- The VHL tumor suppressor at the crossroad of protein folding, aggregation, and cancer.Molecular oncology · 2026Review
- Two decades of research on drug resistance in renal cell carcinoma.Discover oncology · 2026Article
- The advantages and challenges of sorafenib combination therapy: Drug resistance, toxicity and future directions (Review).Oncology letters · 2025Review
- Differential Protein and Glycan Packaging into Extracellular Vesicles in Response to 3D Gastric Cancer Cellular Organization.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Using RNA-seq to identify suitable housekeeping genes for hypoxia studies in human adipose-derived stem cells.BMC molecular and cell biology · 2023Article
- A Hypoxia-Related Signature for Predicting Prognosis, Cellular Processes, Immune Microenvironment and Targeted Compounds in Lung Squamous Cell Carcinoma.International journal of general medicine · 2022Article
- Advances in Renal Cell Carcinoma Drug Resistance Models.Frontiers in oncology · 2022Review
- Prolonged hypoxia switched on cancer stem cell-like plasticity in HepG2 tumourspheres cultured in serum-free media.In vitro cellular & developmental biology. Animal · 2021Article
- An Effective Hypoxia-Related Long Non-Coding RNAs Assessment Model for Prognosis of Clear Cell Renal Carcinoma.Frontiers in oncology · 2021Article
- Renal carcinoma CD105-/CD44- cells display stem-like properties in vitro and form aggressive tumors in vivo.Scientific reports · 2020Article
- Article
- Drug resistance in papillary RCC: from putative mechanisms to clinical practicalities.Nature reviews. Urology · 2019Review
- Development of extracellular matrix supported 3D culture of renal cancer cells and renal cancer stem cells.Cytotechnology · 2019Article
- Activation of c-Met in cancer cells mediates growth-promoting signals against oxidative stress through Nrf2-HO-1.Oncogenesis · 2019Article
- Limitations to the Therapeutic Potential of Tyrosine Kinase Inhibitors and Alternative Therapies for Kidney Cancer.Ochsner journal · 2019Review
- Sorafenib resistance in hepatocarcinoma: role of hypoxia-inducible factors.Experimental & molecular medicine · 2018Review
- Resistance to Systemic Therapies in Clear Cell Renal Cell Carcinoma: Mechanisms and Management Strategies.Molecular cancer therapeutics · 2018Review
- Exploring oncology treatment strategies with tyrosine kinase inhibitors through advanced 3D models (Review).Medicine internationalReview
- The anti-angiogenic tyrosine kinase inhibitor Pazopanib kills cancer cells and disrupts endothelial networks in biomimetic three-dimensional renal tumouroids.Journal of tissue engineeringArticle
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe aim of this study is to determine the effect of hypoxia on axitinib and sorafenib-treated renal cell carcinoma (RCC) cells. Hypoxia is a crucial factor influencing transcription process via protein modulation, which was shown i.e. in pancreatic cancer. Until now, hypoxia has been defined as associated with poorer outcome and inducing chemotherapy resistance in solid tumors. The unique phenomenon of pseudo-hypoxia connected with
resultsClear-cell and papillary renal cell carcinoma (cc and pRCC) cell lines were used in the study to determine the impact of hypoxia on primary drug resistance phenomenon previously observed in papillary, but not in ccRCC. Resistance was confirmed in monolayer culture and in 3D models in soft agar and suspension culture. Human papillary kidney cancer stem-like cells (HKCSCs) cultured in hypoxia developed resistance to sorafenib, while when cultured in normoxia resistance to axitinib has developed. Flow cytometry revealed that hypoxia decreased proliferation rates in all investigated RCC cells. In HKCSCs, there was an increase of quiescent cells (Ki67-) and percentage of cells arrested in S phase. It also appeared that map2k1 and eif4b protein expression is altered in papillary RCC resistant to tested drugs at different oxygen tensions. Also, HKCSCs did not express
conclusionsThe results confirm that low oxygen tension affects RCC cells. Hypoxia facilitates induction of sorafenib resistance in pRCC and induces map2k1 overexpression, while normoxic axitinib-resistant cells up-regulated eif4b. Further studies may determine if map2k1 or eif4b proteins play a role in pRCC resistance to TKIs. It is also of interest to establish if other than
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