Literature DB >> 33510128

Extracellular vesicles-released parathyroid hormone-related protein from Lewis lung carcinoma induces lipolysis and adipose tissue browning in cancer cachexia.

Wenjun Hu1, Hairong Xiong1, Zeyuan Ru1, Yan Zhao1, Yali Zhou1, Kairu Xie1, Wen Xiao2, Zhiyong Xiong2, Cheng Wang2, Changfei Yuan2, Jian Shi2, Quansheng Du3, Xiaoping Zhang2, Hongmei Yang4.   

Abstract

Cancer cachexia is a metabolic disorder characterized by skeletal muscle wasting and white adipose tissue browning. Specific functions of several hormones, growth factors, and cytokines derived from tumors can trigger cachexia. Moreover, adipose tissue lipolysis might explain weight loss that occurs owing to cachexia. Extracellular vesicles (EVs) are involved in intercellular communication. However, whether EVs participate in lipolysis induced by cancer cachexia has not been thoroughly investigated. Using Lewis lung carcinoma (LLC) cell culture, we tested whether LLC cell-derived EVs can induce lipolysis in 3T3-L1 adipocytes. EVs derived from LLC cells were isolated and characterized biochemically and biophysically. Western blotting and glycerol assay were used to study lipolysis. LLC cell-derived EVs induced lipolysis in vivo and vitro. EVs fused directly with target 3T3-L1 adipocytes and transferred parathyroid hormone-related protein (PTHrP), activating the PKA signaling pathway in 3T3-L1 adipocytes. Blocking PTHrP activity in LLC-EVs using a neutralizing antibody and by knocking down PTHR expression prevented lipolysis in adipocytes. Inhibiting the PKA signaling pathway also prevents the lipolytic effects of EVs. In vivo, suppression of LLC-EVs release by knocking down Rab27A alleviated white adipose tissue browning and lipolysis. Our data showed that LLC cell-derived EVs induced adipocyte lipolysis via the extracellular PTHrP-mediated PKA pathway. Our data demonstrate that LLC-EVs induce lipolysis in vitro and vivo by delivering PTHrP, which interacts with PTHR. The lipolytic effect of LLC-EVs was abrogated by PTHR knockdown and treatment with a neutralizing anti-PTHrP antibody. Together, these data show that LLC-EV-induced lipolysis is mediated by extracellular PTHrP. These findings suggest a novel mechanism of lipid droplet loss and identify a potential therapeutic strategy for cancer cachexia.

Entities:  

Year:  2021        PMID： 33510128      PMCID： PMC7843996          DOI： 10.1038/s41419-020-03382-0

Source DB:  PubMed          Journal:  Cell Death Dis            Impact factor:   8.469


  43 in total

1.  Inhibition of oncogenic epidermal growth factor receptor kinase triggers release of exosome-like extracellular vesicles and impacts their phosphoprotein and DNA content.

Authors:  Laura Montermini; Brian Meehan; Delphine Garnier; Wan Jin Lee; Tae Hoon Lee; Abhijit Guha; Khalid Al-Nedawi; Janusz Rak
Journal:  J Biol Chem       Date:  2015-08-13       Impact factor: 5.157

2.  A switch from white to brown fat increases energy expenditure in cancer-associated cachexia.

Authors:  Michele Petruzzelli; Martina Schweiger; Renate Schreiber; Ramon Campos-Olivas; Maria Tsoli; John Allen; Michael Swarbrick; Stefan Rose-John; Mercedes Rincon; Graham Robertson; Rudolf Zechner; Erwin F Wagner
Journal:  Cell Metab       Date:  2014-07-17       Impact factor: 27.287

3.  Reduced adipogenesis after lung tumor exosomes priming in human mesenchymal stem cells via TGFβ signaling pathway.

Authors:  Shihua Wang; Xiaoxia Li; Meiqian Xu; Jing Wang; Robert Chunhua Zhao
Journal:  Mol Cell Biochem       Date:  2017-05-18       Impact factor: 3.396

4.  Lipolysis and lipid oxidation in weight-losing cancer patients and healthy subjects.

Authors:  S D Zuijdgeest-van Leeuwen; J W van den Berg; J L Wattimena; A van der Gaast; G R Swart; J H Wilson; P C Dagnelie
Journal:  Metabolism       Date:  2000-07       Impact factor: 8.694

Review 5.  Parathyroid hormone stimulates adipose tissue browning: a pathway to muscle wasting.

Authors:  Sandhya S Thomas; William E Mitch
Journal:  Curr Opin Clin Nutr Metab Care       Date:  2017-05       Impact factor: 4.294

6.  Lipolysis--not inflammation, cell death, or lipogenesis--is involved in adipose tissue loss in cancer cachexia.

Authors:  Mikael Rydén; Thorhallur Agustsson; Jurga Laurencikiene; Tom Britton; Eva Sjölin; Bengt Isaksson; Johan Permert; Peter Arner
Journal:  Cancer       Date:  2008-10-01       Impact factor: 6.860

Review 7.  Extracellular Vesicles in Cancer: Cell-to-Cell Mediators of Metastasis.

Authors:  Annette Becker; Basant Kumar Thakur; Joshua Mitchell Weiss; Han Sang Kim; Hector Peinado; David Lyden
Journal:  Cancer Cell       Date:  2016-12-12       Impact factor: 31.743

8.  miR-34c-5p promotes eradication of acute myeloid leukemia stem cells by inducing senescence through selective RAB27B targeting to inhibit exosome shedding.

Authors:  Danyue Peng; Huifang Wang; Lei Li; Xiao Ma; Ying Chen; Hao Zhou; Yi Luo; Yin Xiao; Lingbo Liu
Journal:  Leukemia       Date:  2018-02-02       Impact factor: 11.528

9.  Quantification of plasma exosome is a potential prognostic marker for esophageal squamous cell carcinoma.

Authors:  Yasunori Matsumoto; Masayuki Kano; Yasunori Akutsu; Naoyuki Hanari; Isamu Hoshino; Kentaro Murakami; Akihiro Usui; Hiroshi Suito; Masahiko Takahashi; Ryota Otsuka; Hu Xin; Aki Komatsu; Keiko Iida; Hisahiro Matsubara
Journal:  Oncol Rep       Date:  2016-09-05       Impact factor: 3.906

10.  Tumor induces muscle wasting in mice through releasing extracellular Hsp70 and Hsp90.

Authors:  Guohua Zhang; Zhelong Liu; Hui Ding; Yong Zhou; Hoang Anh Doan; Ka Wai Thomas Sin; Zhiren J Zhu; Rene Flores; Yefei Wen; Xing Gong; Qingyun Liu; Yi-Ping Li
Journal:  Nat Commun       Date:  2017-09-19       Impact factor: 14.919
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  8 in total

1.  Early-Onset Physical Inactivity and Metabolic Dysfunction in Tumor-bearing Mice Is Associated with Accelerated Cachexia.

Authors:  Brittany R Counts; Jessica L Halle; James A Carson
Journal:  Med Sci Sports Exerc       Date:  2022-01-01       Impact factor: 5.411

2.  Tumor cell anabolism and host tissue catabolism-energetic inefficiency during cancer cachexia.

Authors:  Mangala Hegde; Uzini Devi Daimary; Sosmitha Girisa; Aviral Kumar; Ajaikumar B Kunnumakkara
Journal:  Exp Biol Med (Maywood)       Date:  2022-05-06

Review 3.  Metabolic Reprogramming in Adipose Tissue During Cancer Cachexia.

Authors:  Bahar Zehra Camurdanoglu Weber; Dilsad H Arabaci; Serkan Kir
Journal:  Front Oncol       Date:  2022-05-12       Impact factor: 5.738

Review 4.  Role of myokines and osteokines in cancer cachexia.

Authors:  Fabrizio Pin; Lynda F Bonewald; Andrea Bonetto
Journal:  Exp Biol Med (Maywood)       Date:  2021-04-25

5.  Whole-body and adipose tissue metabolic phenotype in cancer patients.

Authors:  Lindsey J Anderson; Jonathan Lee; Barbara Anderson; Benjamin Lee; Dorota Migula; Adam Sauer; Nicole Chong; Haiming Liu; Peter C Wu; Atreya Dash; Yi-Ping Li; Jose M Garcia
Journal:  J Cachexia Sarcopenia Muscle       Date:  2022-01-28       Impact factor: 12.063

6.  Inhibition of epidermal growth factor receptor suppresses parathyroid hormone-related protein expression in tumours and ameliorates cancer-associated cachexia.

Authors:  Bahar Zehra Camurdanoglu Weber; Samet Agca; Aylin Domaniku; Sevval Nur Bilgic; Dilsad H Arabaci; Serkan Kir
Journal:  J Cachexia Sarcopenia Muscle       Date:  2022-04-04       Impact factor: 12.063

Review 7.  The evolving view of thermogenic fat and its implications in cancer and metabolic diseases.

Authors:  Xinpeng Yin; Yuan Chen; Rexiati Ruze; Ruiyuan Xu; Jianlu Song; Chengcheng Wang; Qiang Xu
Journal:  Signal Transduct Target Ther       Date:  2022-09-16

Review 8.  Targeting cancer cachexia: Molecular mechanisms and clinical study.

Authors:  Yong-Fei Wang; Zi-Yi An; Dong-Hai Lin; Wei-Lin Jin
Journal:  MedComm (2020)       Date:  2022-09-10
  8 in total

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