Secretome from Magnetically Stimulated Muscle Exhibits Anticancer Potency: Novel Preconditioning Methodology Highlighting HTRA1 Action

Tai, Yee Kit; Iversen, Jan Nikolas; Chan, Karen Ka Wing; Fong, Charlene Hui Hua; Abdul Razar, Rafhanah Banu; Ramanan, Sharanya; Yap, Lye Yee Jasmine; Yin, Jocelyn Naixin; Toh, Shi Jie; Wong, Craig Jun Kit; Koh, Pei Fern Angele; Huang, Ruby Yun Ju; Franco-Obregón, Alfredo

doi:10.3390/cells13050460

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Secretome from Magnetically Stimulated Muscle Exhibits Anticancer Potency: Novel Preconditioning Methodology Highlighting HTRA1 Action

by

Yee Kit Tai

^{1,2,3,4,*,†}

,

Jan Nikolas Iversen

^1,2,3,†

,

Karen Ka Wing Chan

^1,2,3,†,

Charlene Hui Hua Fong

^1,2,3,

Rafhanah Banu Abdul Razar

^1,2,3,

Sharanya Ramanan

^1,2,3,

Lye Yee Jasmine Yap

^1,2,3,

Jocelyn Naixin Yin

^1,2,3,

Shi Jie Toh

^1,2,3,

Craig Jun Kit Wong

^1,2,3,

Pei Fern Angele Koh

⁵,

Ruby Yun Ju Huang

^5,6,7,8

and

Alfredo Franco-Obregón

^{1,2,3,4,9,10,11,*}

¹

Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore

²

Institute of Health Technology and Innovation (iHealthtech), National University of Singapore, Singapore 117599, Singapore

³

Biolonic Currents Electromagnetic Pulsing Systems Laboratory (BICEPS), National University of Singapore, Singapore 117599, Singapore

⁴

NUS Centre for Cancer Research, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore

⁵

Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore

⁶

Department of Obstetrics & Gynaecology, National University of Singapore, Singapore 119228, Singapore

⁷

Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei 10617, Taiwan

⁸

School of Medicine, College of Medicine, National Taiwan University, Taipei 10617, Taiwan

⁹

Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore

¹⁰

Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117593, Singapore

¹¹

Competence Center for Applied Biotechnology and Molecular Medicine, University of Zürich, 8057 Zürich, Switzerland

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^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Cells 2024, 13(5), 460; https://doi.org/10.3390/cells13050460

Submission received: 31 January 2024 / Revised: 27 February 2024 / Accepted: 4 March 2024 / Published: 5 March 2024

(This article belongs to the Special Issue Advances in Muscle Research in Health and Disease)

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Abstract

Briefly (10 min) exposing C2C12 myotubes to low amplitude (1.5 mT) pulsed electromagnetic fields (PEMFs) generated a conditioned media (pCM) that was capable of mitigating breast cancer cell growth, migration, and invasiveness in vitro, whereas the conditioned media harvested from unexposed myotubes, representing constitutively released secretome (cCM), was less effective. Administering pCM to breast cancer microtumors engrafted onto the chorioallantoic membrane of chicken eggs reduced tumor volume and vascularity. Blood serum collected from PEMF-exposed or exercised mice allayed breast cancer cell growth, migration, and invasiveness. A secretome preconditioning methodology is presented that accentuates the graded anticancer potencies of both the cCM and pCM harvested from myotubes, demonstrating an adaptive response to pCM administered during early myogenesis that emulated secretome-based exercise adaptations observed in vivo. HTRA1 was shown to be upregulated in pCM and was demonstrated to be necessary and sufficient for the anticancer potency of the pCM; recombinant HTRA1 added to basal media recapitulated the anticancer effects of pCM and antibody-based absorption of HTRA1 from pCM precluded its anticancer effects. Brief and non-invasive PEMF stimulation may represent a method to commandeer the secretome response of muscle, both in vitro and in vivo, for clinical exploitation in breast and other cancers.

Keywords: exercise; breast cancer; myokines; exerkines; proteomics; PEMFs; conditioned media; soluble biomarkers; metastasis; aminoglycoside antibiotics

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MDPI and ACS Style

Tai, Y.K.; Iversen, J.N.; Chan, K.K.W.; Fong, C.H.H.; Abdul Razar, R.B.; Ramanan, S.; Yap, L.Y.J.; Yin, J.N.; Toh, S.J.; Wong, C.J.K.; et al. Secretome from Magnetically Stimulated Muscle Exhibits Anticancer Potency: Novel Preconditioning Methodology Highlighting HTRA1 Action. Cells 2024, 13, 460. https://doi.org/10.3390/cells13050460

AMA Style

Tai YK, Iversen JN, Chan KKW, Fong CHH, Abdul Razar RB, Ramanan S, Yap LYJ, Yin JN, Toh SJ, Wong CJK, et al. Secretome from Magnetically Stimulated Muscle Exhibits Anticancer Potency: Novel Preconditioning Methodology Highlighting HTRA1 Action. Cells. 2024; 13(5):460. https://doi.org/10.3390/cells13050460

Chicago/Turabian Style

Tai, Yee Kit, Jan Nikolas Iversen, Karen Ka Wing Chan, Charlene Hui Hua Fong, Rafhanah Banu Abdul Razar, Sharanya Ramanan, Lye Yee Jasmine Yap, Jocelyn Naixin Yin, Shi Jie Toh, Craig Jun Kit Wong, and et al. 2024. "Secretome from Magnetically Stimulated Muscle Exhibits Anticancer Potency: Novel Preconditioning Methodology Highlighting HTRA1 Action" Cells 13, no. 5: 460. https://doi.org/10.3390/cells13050460

APA Style

Tai, Y. K., Iversen, J. N., Chan, K. K. W., Fong, C. H. H., Abdul Razar, R. B., Ramanan, S., Yap, L. Y. J., Yin, J. N., Toh, S. J., Wong, C. J. K., Koh, P. F. A., Huang, R. Y. J., & Franco-Obregón, A. (2024). Secretome from Magnetically Stimulated Muscle Exhibits Anticancer Potency: Novel Preconditioning Methodology Highlighting HTRA1 Action. Cells, 13(5), 460. https://doi.org/10.3390/cells13050460

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Secretome from Magnetically Stimulated Muscle Exhibits Anticancer Potency: Novel Preconditioning Methodology Highlighting HTRA1 Action

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