Dataset Information

Exercise forms a metabolic-shield in distant organs blocking cancer progression and metastatic dissemination-Part 1

ABSTRACT: Exercise prevents cancer incidence and recurrence, yet the underlying mechanism remains mostly unknown. Here we report that exercise induces a metabolic reprogramming of internal organs, increasing their nutrient demand, thus protecting them against metastatic colonization by limiting nutrient availability to the tumor, which we termed exercise induced metabolic-shield. Proteomic and ex-vivo metabolic-capacity analyses of mice internal organs revealed that exercise induces catabolic processes, glucose uptake, mitochondrial activity, and GLUT expression. Proteomic analysis of routinely active subjects' plasma demonstrated increased carbohydrate utilization following exercise. Further, epidemiological data of a 20-year follow-up of a large human cohort of cancer free participants, revealed that exercise prior to cancer initiation has a modest impact on cancer incidence in low metastatic stages, but significantly reduced the likelihood of highly metastatic cancer as compared to inactive participants. We utilized two exercise protocols, wherein the mice were subjected to exercise either both pre- and post- melanoma injection or only pre-injection. We found that exercise prior to cancer injection significantly protects against metastases in distant organs, regardless of the three melanoma metastases models we used. Mechanistically, ex-vivo inhibition of the mTOR pathway, via rapamycin treatment, reversed the protection from the exercise induced metabolic-shield. Under limited glucose conditions, active stroma consumed significantly more glucose, at the expense of the tumor, as reflected in histology analyses of mice melanoma metastases. Our data suggests that cancers’ metabolic plasticity and the exercise-induced metabolic reprogramming of the stroma are clashing, raising the opportunity to block metastases by challenging cancers’ metabolic needs.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Lung, Liver, Lymph Node

SUBMITTER: Tamar Ziv

LAB HEAD: Carmit Levy

PROVIDER: PXD035630 | Pride | 2023-03-11

REPOSITORIES: Pride

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An Exercise-Induced Metabolic Shield in Distant Organs Blocks Cancer Progression and Metastatic Dissemination.

Sheinboim Danna D Parikh Shivang S Manich Paulee P Markus Irit I Dahan Sapir S Parikh Roma R Stubbs Elisa E Cohen Gali G Zemser-Werner Valentina V Bell Rachel E RE Ruiz Sara Arciniegas SA Percik Ruth R Brenner Ronen R Leibou Stav S Vaknine Hananya H Arad Gali G Gerber Yariv Y Keinan-Boker Lital L Shimony Tal T Bikovski Lior L Goldstein Nir N Constantini Keren K Labes Sapir S Mordechai Shimonov S Doron Hila H Lonescu Ariel A Ziv Tamar T Nizri Eran E Choshen Guy G Eldar-Finkelman Hagit H Tabach Yuval Y Helman Aharon A Ben-Eliyahu Shamgar S Erez Neta N Perlson Eran E Geiger Tamar T Ben-Zvi Danny D Khaled Mehdi M Gepner Yftach Y Levy Carmit C

Cancer research 20221101 22

Exercise prevents cancer incidence and recurrence, yet the underlying mechanism behind this relationship remains mostly unknown. Here we report that exercise induces the metabolic reprogramming of internal organs that increases nutrient demand and protects against metastatic colonization by limiting nutrient availability to the tumor, generating an exercise-induced metabolic shield. Proteomic and ex vivo metabolic capacity analyses of murine internal organs revealed that exercise induces catabol ...[more]

PMID: 36084256

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			Action	DRS
	51430_liver_txt.rar	Other
	51438_muscle_txt.rar	Other
	51446_lymph_txt.rar	Other
	51454_Lung_txt.rar	Other
	Seq51430_QE2.raw	Raw