Running reverses tumor-induced muscle weakness in mice with breast cancer

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Lanner, JohannaKarolinska Institutet, Stockholm, Sweden (author)

Running reverses tumor-induced muscle weakness in mice with breast cancer

Article/chapterEnglish2019

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2019
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LIBRIS-ID:oai:DiVA.org:oru-77141
https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-77141URI

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Language:English
Summary in:English

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SwePubSwePub

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Subject category:ref swepub-contenttype
Subject category:kon swepub-publicationtype

Notes

Introduction: Patients with breast cancer experience muscle dysfunction, which is a clinical challenge that is not restricted to advanced stage patients, but also observed in newly diagnosed weight-stable patients with low tumor burden. Recent data indicate that physical activity can reduce breast cancerassociated mortality, suggesting that improved muscle performance per secan have positive impact on survival. Here, the transgenic PyMT mouse model of breast cancer was used to elucidate molecular mechanisms underlying breast cancer-induced muscle impairments.Materials and Methods: PyMT mice and wildtype (WT) littermates w/wo access to an in-cage running wheel for four weeks (week 8-12). Functional readouts included Ca2+imaging; isometric force measurement on single fibers and intact fast-and slow-twitchmuscles. Intramuscular signaling was assessed using immunofluorescence, immunoblotting and enzymatic assays.Results: The specific force (i.e. force/cross-sectional area) was significantly decreased by ~ 35% in slow-twitch soleus muscles from breast cancermice as compared to WT muscles, which was the result of reduced Ca2+release and impaired myofibrillar function. There were no difference in muscle size or fiber type between the two groups. However, higher intramuscular stress (e.g. p38 activation and carbonylation (DNP)) was observed in PyMT than in WT. Intriguingly, voluntary running for four weeks reversed the weakness and PyMT soleus muscles generated similar forces as muscles of exercised WT mice. The running induced higher SOD2 expression and normalized levels of p38 and DNP.Conclusion: Intrinsic contractile dysfunction and higher intramuscular stress was present in mice with breast cancer, which was counteracted with voluntary running.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Fysiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Physiology hsv//eng
Sports Science
Idrottsvetenskap

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Mader, TheresaKarolinska Institutet, Stockholm, Sweden (author)
Chaillou, Thomas,1985-Örebro universitet,Institutionen för hälsovetenskaper,Karolinska institutet, Stockholm, Sweden(Swepub:oru)tcu (author)
Cheng, ArthurKarolinska Institutet, Stockholm, Sweden (author)
Steinz, MarteenKarolinska Institutet, Stockholm, Sweden (author)
Zhengye, LiuKarolinska Institutet, Stockholm, Sweden (author)
Rundqvist, HeleneKarolinska Institutet, Stockholm, Sweden (author)
Kenne, ElinorKarolinska Institutet, Stockholm, Sweden (author)
Karolinska Institutet, Stockholm, SwedenInstitutionen för hälsovetenskaper (creator_code:org_t)

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By the author/editor: Lanner, Johanna; Mader, Theresa; Chaillou, Thomas ...; Cheng, Arthur; Steinz, Marteen; Zhengye, Liu; show more...; Rundqvist, Helen ...; Kenne, Elinor; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Physiology

By the university: Örebro University

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