Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Jan;129(1):80-92.
doi: 10.1111/bju.15506. Epub 2021 Aug 8.

Cancer-associated fibroblasts in renal cell carcinoma: implication in prognosis and resistance to anti-angiogenic therapy

Damien Ambrosetti  1   2 , Michael Coutts  3 , Charlotte Paoli  1 , Matthieu Durand  4 , Delphine Borchiellini  5 , Christopher Montemagno  2   6   7 , Olivia Rastoin  2   7 , Arnaud Borderie  1 , Renaud Grepin  6   7 , Nathalie Rioux-Leclercq  8 , Jean-Christophe Bernhard  9   10 , Gilles Pagès  2   6   7 , Maeva Dufies  6   7
Affiliations
Free article

Cancer-associated fibroblasts in renal cell carcinoma: implication in prognosis and resistance to anti-angiogenic therapy

Damien Ambrosetti et al. BJU Int. 2022 Jan.
Free article

Abstract

Objectives: To investigate the role of cancer-associated fibroblasts (CAFs) in clear cell renal cell carcinoma (ccRCC) with respect to tumour aggressiveness, metastasis development, and resistance to anti-angiogenic therapy (vascular endothelial growth factor receptor-tyrosine kinase inhibitors [VEGFR-TKI]).

Patients and methods: Our study involved tissue samples from three distinct and independent cohorts of patients with ccRCC. The presence of CAFs and tumour lymphangiogenesis was investigated, respectively, by transcriptional signatures and then correlated with tumour development and prognosis. The effect of these CAFs on tumour cell migration and VEGFR-TKI resistance was analysed on co-cultures of ccRCC cells with CAFs.

Results: Results from our cohorts and from in silico investigations showed that VEGFR-TKI significantly increase the number of CAFs in tumours. In the same populations of patients with ccRCC, the proportion of intra-tumoral CAFs correlated to shorter disease-free and overall survival. The presence of CAFs was also correlated with lymphangiogenesis and lymph node metastasis. CAFs increased the migration and decreased the VEGFR-TKI-dependent cytotoxic effect of tumour cells.

Conclusions: Our results show that VEGFR-TKI promote the development of CAFs, and CAFs favour tumour aggressiveness, metastatic dissemination, and resistance to treatment in ccRCC. CAFs could represent a new therapeutic target to fight resistance to treatment of ccRCC. Targeting CAF and immunotherapies combination are emerging as efficient treatments in many types of solid tumours. Our results highlight their relevance in ccRCC.

Keywords: #KidneyCancer; #kcsm; #uroonc; anti-angiogenic treatment; cancer-associated fibroblasts; clear cell renal cell carcinoma; fibroblast-associated protein; prognostic marker; resistance.

PubMed Disclaimer

References

    1. Palumbo C, Pecoraro A, Knipper S et al. Contemporary age-adjusted incidence and mortality rates of renal cell carcinoma: analysis according to gender, race, stage, grade, and histology. Eur Urol Focus 2020. https://doi.org/10.1016/j.euf.2020.05.003.
    1. Moch H, Cubilla AL, Humphrey PA, Reuter VE, Ulbright TM. The 2016 WHO classification of tumours of the urinary system and male genital organs-part A: renal, penile, and testicular tumours. Eur Urol 2016; 70: 93-105
    1. Ljungberg B, Albiges L, Abu-Ghanem Y et al. European association of urology guidelines on renal cell carcinoma: the 2019 update. Eur Urol 2019; 75: 799-810
    1. Atkins MB, Tannir NM. Current and emerging therapies for first-line treatment of metastatic clear cell renal cell carcinoma. Cancer Treat Rev 2018; 70: 127-37
    1. Rini BI, Atkins MB. Resistance to targeted therapy in renal-cell carcinoma. Lancet Oncol 2009; 10: 992-1000

Publication types

MeSH terms