The thermogenic activity of adjacent adipocytes fuels the progression of ccRCC and compromises anti-tumor therapeutic efficacy.

Adipocytes / metabolism Carcinoma, Renal Cell / pathology Cell Line, Tumor Humans Kidney Neoplasms / pathology Sunitinib / pharmacology Thermogenesis
PKA PTHrP adipocytes browning cell-to-cell communication clear cell renal cell carcinoma lactate lung metastasis tyrosine kinase inhibitors

Journal

Cell metabolism
ISSN: 1932-7420
Titre abrégé: Cell Metab
Pays: United States
ID NLM: 101233170

Informations de publication

Date de publication:
05 10 2021
Historique:
received: 28 07 2020
revised: 08 07 2021
accepted: 17 08 2021
pubmed: 12 9 2021
medline: 8 4 2022
entrez: 11 9 2021
Statut: ppublish

Résumé

Clear cell renal cell carcinoma (ccRCC) preferentially invades into perinephric adipose tissue (PAT), a process associated with poor prognosis. However, the detailed mechanisms underlying this interaction remain elusive. Here, we describe a bi-directional communication between ccRCC cells and the PAT. We found that ccRCC cells secrete parathyroid-hormone-related protein (PTHrP) to promote the browning of PAT by PKA activation, while PAT-mediated thermogenesis results in the release of excess lactate to enhance ccRCC growth, invasion, and metastasis. Further, tyrosine kinase inhibitors (TKIs) extensively used in the treatment of ccRCC enhanced this vicious cycle of ccRCC-PAT communication by promoting the browning of PAT. However, if this cross-communication was short circuited by the pharmacological suppression of adipocyte browning via H89 or KT5720, the anti-tumor efficacy of the TKI, sunitinib, was enhanced. These results suggest that ccRCC-PAT cross-communication has important clinical relevance, and use of combined therapy holds great promise in enhancing the efficacy of TKIs.

Identifiants

DOI: 10.1016/j.cmet.2021.08.012 PMID: 34508696
pubmed: 34508696
pii: S1550-4131(21)00375-2
doi: 10.1016/j.cmet.2021.08.012
pii:
doi:

Substances chimiques

Sunitinib V99T50803M

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2021-2039.e8

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2021 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests J. Liu has filed a provisional pending patent (CNIPA; patent number: 202010437336.X) regarding treatment of ccRCC tumors with the combination of sunitinib and H89.

Auteurs

Gang Wei (G)

Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China.

Honglin Sun (H)

Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China.

Kai Dong (K)

Department of Urology, Changhai Hospital, Naval Medical University, Shanghai 200433, China.

Libing Hu (L)

Department of Urology, Yan'an Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650051, China.

Qi Wang (Q)

State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Metabonomics and Systems Biology Laboratory at Shanghai International Centre for Molecular Phenomics, Zhongshan Hospital, Fudan University, Shanghai 200438, China.

Qian Zhuang (Q)

State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China.

Yan Zhu (Y)

Department of Urology, Changhai Hospital, Naval Medical University, Shanghai 200433, China.

Xianjing Zhang (X)

Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China.

Yaodi Shao (Y)

Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China.

Huiru Tang (H)

State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Metabonomics and Systems Biology Laboratory at Shanghai International Centre for Molecular Phenomics, Zhongshan Hospital, Fudan University, Shanghai 200438, China.

Zhenfei Li (Z)

State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China.

Suzhen Chen (S)

Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China.

Junxi Lu (J)

Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China.

Yibing Wang (Y)

School of Kinesiology, Shanghai University of Sport, Shanghai 200438, China.

Xinxin Gan (X)

Department of Urology, Changhai Hospital, Naval Medical University, Shanghai 200433, China.

Tao P Zhong (TP)

Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, China.

Dingkun Gui (D)

Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China.

Xiaoyong Hu (X)

Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China.

Linhui Wang (L)

Department of Urology, Changhai Hospital, Naval Medical University, Shanghai 200433, China. Electronic address: wanglinhui@smmu.edu.cn.

Junli Liu (J)

Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China. Electronic address: liujunli@sjtu.edu.cn.

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Classifications MeSH

questionsmedicales.fr › Cellules › Cellules du tissu conjonctif › Adipocytes › The thermogenic activity of adjacent...
questionsmedicales.fr › Maladies urogénitales › Maladies urologiques › Tumeurs urologiques › Tumeurs du rein › Néphrocarcinome › The thermogenic activity of adjacent...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › The thermogenic activity of adjacent...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › The thermogenic activity of adjacent...
questionsmedicales.fr › Maladies urogénitales › Maladies urologiques › Tumeurs urologiques › Tumeurs du rein › The thermogenic activity of adjacent...
questionsmedicales.fr › Composés hétérocycliques › Composés hétérocycliques à cycles fusionnés › Composés hétérobicycliques › Indoles › Sunitinib › The thermogenic activity of adjacent...
questionsmedicales.fr › Phénomènes biologiques › Adaptation biologique › Adaptation physiologique › Régulation de la température corporelle › Thermogenèse › The thermogenic activity of adjacent...