Secretome from Magnetically Stimulated Muscle Exhibits Anticancer Potency: Novel Preconditioning Methodology Highlighting HTRA1 Action
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Culture and Chemical Reagents
2.2. Generation of Muscle-Conditioned Media
2.3. Cancer Cell Count, Colony Formation, Invasion and Migration Assays
2.4. HTRA1-Depletion Conditioned Media
2.5. Chicken Chorioallantoic Membrane (CAM) Model and Ultrasound Assessment
2.6. Myotube Differentiation and Preconditioning Paradigm
2.7. Western Blot and Silencing of HTRA1
2.8. Animal Study Protocol and Serum ELISA
2.9. Statistical Analyses
3. Results
3.1. PEMF-Conditioned Media (pCM) Inhibits Breast Cancer Growth In Vitro and Ex Vivo
3.2. PEMF Treatment of Mice Produces Anticancer Blood Serum
3.3. Preconditioning Paradigm to Accentuate the Anticancer Potency of pCM
3.4. HTRA1 Instigates Preconditioning Efficacy
4. Discussion
4.1. Parallels between PEMF-Exposure and Exercise
4.2. pCM Preconditioning System for Enhanced Secretome Characteristics
4.3. HTRA1 Reinforces Muscular Anticancer Response
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Barbalho, S.M.; Prado Neto, E.V.; De Alvares Goulart, R.; Bechara, M.D.; Baisi Chagas, E.F.; Audi, M.; Guissoni Campos, L.M.; Landgraf Guiger, E.; Buchaim, R.L.; Buchaim, D.V.; et al. Myokines: A descriptive review. J. Sports Med. Phys. Fitness 2020, 60, 1583–1590. [Google Scholar] [CrossRef]
- Artero, E.G.; Lee, D.C.; Lavie, C.J.; Espana-Romero, V.; Sui, X.; Church, T.S.; Blair, S.N. Effects of muscular strength on cardiovascular risk factors and prognosis. J. Cardiopulm. Rehabil. Prev. 2012, 32, 351–358. [Google Scholar] [CrossRef]
- Franco-Obregon, A.; Tai, Y.K.; Wu, K.Y.; Iversen, J.N.; Wong, C.J.K. The Developmental Implications of Muscle-Targeted Magnetic Mitohormesis: A Human Health and Longevity Perspective. Bioengineering 2023, 10, 956. [Google Scholar] [CrossRef]
- Papadopetraki, A.; Maridaki, M.; Zagouri, F.; Dimopoulos, M.A.; Koutsilieris, M.; Philippou, A. Physical Exercise Restrains Cancer Progression through Muscle-Derived Factors. Cancers 2022, 14, 1892. [Google Scholar] [CrossRef]
- Louzada, R.A.; Bouviere, J.; Matta, L.P.; Werneck-de-Castro, J.P.; Dupuy, C.; Carvalho, D.P.; Fortunato, R.S. Redox Signaling in Widespread Health Benefits of Exercise. Antioxid. Redox Signal. 2020, 33, 745–760. [Google Scholar] [CrossRef]
- Scheele, C.; Nielsen, S.; Pedersen, B.K. ROS and myokines promote muscle adaptation to exercise. Trends Endocrinol. Metab. 2009, 20, 95–99. [Google Scholar] [CrossRef]
- Larson, E.A.; Dalamaga, M.; Magkos, F. The role of exercise in obesity-related cancers: Current evidence and biological mechanisms. Semin. Cancer Biol. 2023, 91, 16–26. [Google Scholar] [CrossRef]
- Hoffmann, C.; Weigert, C. Skeletal Muscle as an Endocrine Organ: The Role of Myokines in Exercise Adaptations. Cold Spring Harb. Perspect. Med. 2017, 7, a029793. [Google Scholar] [CrossRef]
- Cannioto, R.A.; Hutson, A.; Dighe, S.; McCann, W.; McCann, S.E.; Zirpoli, G.R.; Barlow, W.; Kelly, K.M.; DeNysschen, C.A.; Hershman, D.L.; et al. Physical activity before, during and after chemotherapy for high-risk breast cancer: Relationships with survival. J. Natl. Cancer Inst. 2021, 113, 54–63. [Google Scholar] [CrossRef]
- Kim, J.S.; Taaffe, D.R.; Galvao, D.A.; Clay, T.D.; Redfern, A.D.; Hart, N.H.; Gray, E.S.; Ryan, C.J.; Kenfield, S.A.; Saad, F.; et al. Acute effect of high-intensity interval aerobic exercise on serum myokine levels and resulting tumour-suppressive effect in trained patients with advanced prostate cancer. Prostate Cancer Prostatic Dis. 2023, 26, 795–801. [Google Scholar] [CrossRef]
- Wang, T.; Zhang, Y.; Taaffe, D.R.; Kim, J.S.; Luo, H.; Yang, L.; Fairman, C.M.; Qiao, Y.; Newton, R.U.; Galvao, D.A. Protective effects of physical activity in colon cancer and underlying mechanisms: A review of epidemiological and biological evidence. Crit. Rev. Oncol. Hematol. 2022, 170, 103578. [Google Scholar] [CrossRef]
- Mijwel, S.; Jervaeus, A.; Bolam, K.A.; Norrbom, J.; Bergh, J.; Rundqvist, H.; Wengstrom, Y. High-intensity exercise during chemotherapy induces beneficial effects 12 months into breast cancer survivorship. J. Cancer Surviv. 2019, 13, 244–256. [Google Scholar] [CrossRef]
- Goh, J.; Tsai, J.; Bammler, T.K.; Farin, F.M.; Endicott, E.; Ladiges, W.C. Exercise training in transgenic mice is associated with attenuation of early breast cancer growth in a dose-dependent manner. PLoS ONE 2013, 8, e80123. [Google Scholar] [CrossRef]
- Hojman, P.; Dethlefsen, C.; Brandt, C.; Hansen, J.; Pedersen, L.; Pedersen, B.K. Exercise-induced muscle-derived cytokines inhibit mammary cancer cell growth. Am. J. Physiol. Endocrinol. Metab. 2011, 301, E504–E510. [Google Scholar] [CrossRef]
- Kim, J.S.; Taaffe, D.R.; Galvao, D.A.; Hart, N.H.; Gray, E.; Ryan, C.J.; Kenfield, S.A.; Saad, F.; Newton, R.U. Exercise in advanced prostate cancer elevates myokine levels and suppresses in-vitro cell growth. Prostate Cancer Prostatic Dis. 2022, 25, 86–92. [Google Scholar] [CrossRef]
- Schwappacher, R.; Dieterich, W.; Reljic, D.; Pilarsky, C.; Mukhopadhyay, D.; Chang, D.K.; Biankin, A.V.; Siebler, J.; Herrmann, H.J.; Neurath, M.F.; et al. Muscle-Derived Cytokines Reduce Growth, Viability and Migratory Activity of Pancreatic Cancer Cells. Cancers 2021, 13, 3820. [Google Scholar] [CrossRef]
- Baldelli, G.; De Santi, M.; Gervasi, M.; Annibalini, G.; Sisti, D.; Hojman, P.; Sestili, P.; Stocchi, V.; Barbieri, E.; Brandi, G. The effects of human sera conditioned by high-intensity exercise sessions and training on the tumorigenic potential of cancer cells. Clin. Transl. Oncol. 2021, 23, 22–34. [Google Scholar] [CrossRef]
- Dethlefsen, C.; Lillelund, C.; Midtgaard, J.; Andersen, C.; Pedersen, B.K.; Christensen, J.F.; Hojman, P. Exercise regulates breast cancer cell viability: Systemic training adaptations versus acute exercise responses. Breast Cancer Res. Treat. 2016, 159, 469–479. [Google Scholar] [CrossRef]
- Yip, C.H.; Bhoo Pathy, N.; Teo, S.H. A review of breast cancer research in malaysia. Med. J. Malaysia 2014, 69 (Suppl. A), 8–22. [Google Scholar]
- Chow, L.S.; Gerszten, R.E.; Taylor, J.M.; Pedersen, B.K.; van Praag, H.; Trappe, S.; Febbraio, M.A.; Galis, Z.S.; Gao, Y.; Haus, J.M.; et al. Exerkines in health, resilience and disease. Nat. Rev. Endocrinol. 2022, 18, 273–289. [Google Scholar] [CrossRef]
- Park, S.Y.; Hwang, B.O.; Song, N.Y. The role of myokines in cancer: Crosstalk between skeletal muscle and tumor. BMB Rep. 2023, 56, 365–373. [Google Scholar] [CrossRef]
- Alizadeh Zarei, M.; Seyed Hosseini, E.; Haddad Kashani, H.; Ahmad, E.; Nikzad, H. Effects of the exercise-inducible myokine irisin on proliferation and malignant properties of ovarian cancer cells through the HIF-1 alpha signaling pathway. Sci. Rep. 2023, 13, 170. [Google Scholar] [CrossRef]
- Tai, Y.K.; Ng, C.; Purnamawati, K.; Yap, J.L.Y.; Yin, J.N.; Wong, C.; Patel, B.K.; Soong, P.L.; Pelczar, P.; Frohlich, J.; et al. Magnetic fields modulate metabolism and gut microbiome in correlation with Pgc-1alpha expression: Follow-up to an in vitro magnetic mitohormetic study. FASEB J. 2020, 34, 11143–11167. [Google Scholar] [CrossRef]
- Yap, J.L.Y.; Tai, Y.K.; Fröhlich, J.; Fong, C.H.H.; Yin, J.N.; Foo, Z.L.; Ramanan, S.; Beyer, C.; Toh, S.J.; Casarosa, M.; et al. Ambient and supplemental magnetic fields promote myogenesis via a TRPC1-mitochondrial axis: Evidence of a magnetic mitohormetic mechanism. FASEB J. 2019, 33, 12853–12872. [Google Scholar] [CrossRef]
- Wong, C.J.K.; Tai, Y.K.; Yap, J.L.Y.; Fong, C.H.H.; Loo, L.S.W.; Kukumberg, M.; Frohlich, J.; Zhang, S.; Li, J.Z.; Wang, J.W.; et al. Brief exposure to directionally-specific pulsed electromagnetic fields stimulates extracellular vesicle release and is antagonized by streptomycin: A potential regenerative medicine and food industry paradigm. Biomaterials 2022, 287, 121658. [Google Scholar] [CrossRef]
- Venugobal, S.; Tai, Y.K.; Goh, J.; Teh, S.; Wong, C.; Goh, I.; Maier, A.B.; Kennedy, B.K.; Franco-Obregon, A. Brief, weekly magnetic muscle therapy improves mobility and lean body mass in older adults: A Southeast Asia community case study. Aging 2023, 15, 1768–1790. [Google Scholar] [CrossRef]
- Stephenson, M.C.; Krishna, L.; Pannir Selvan, R.M.; Tai, Y.K.; Kit Wong, C.J.; Yin, J.N.; Toh, S.J.; Torta, F.; Triebl, A.; Fröhlich, J.; et al. Magnetic field therapy enhances muscle mitochondrial bioenergetics and attenuates systemic ceramide levels following ACL reconstruction: Southeast Asian randomized-controlled pilot trial. J. Orthop. Transl. 2022, 35, 99–112. [Google Scholar] [CrossRef]
- Tiaden, A.N.; Richards, P.J. The emerging roles of HTRA1 in musculoskeletal disease. Am. J. Pathol. 2013, 182, 1482–1488. [Google Scholar] [CrossRef]
- Chen, M.; Yang, S.; Wu, Y.; Zhao, Z.; Zhai, X.; Dong, D. High temperature requirement A1 in cancer: Biomarker and therapeutic target. Cancer Cell Int. 2021, 21, 513. [Google Scholar] [CrossRef]
- Chien, J.; Campioni, M.; Shridhar, V.; Baldi, A. HtrA serine proteases as potential therapeutic targets in cancer. Curr. Cancer Drug Targets 2009, 9, 451–468. [Google Scholar] [CrossRef]
- Franco, R.; Collina, F.; Di Bonito, M.; Botti, G.; Montanaro, D.; Di Maio, L.; Vincenzi, B.; Landi, G.; D’Aiuto, M.; Caraglia, M.; et al. HtrA1 loss is related to aggressive behavior parameters in sentinel node positive breast cancer. Histol. Histopathol. 2015, 30, 707–714. [Google Scholar] [CrossRef]
- Tossetta, G.; Fantone, S.; Licini, C.; Marzioni, D.; Mattioli-Belmonte, M. The multifaced role of HtrA1 in the development of joint and skeletal disorders. Bone 2022, 157, 116350. [Google Scholar] [CrossRef]
- Pedersen, B.K.; Febbraio, M.A. Muscle as an endocrine organ: Focus on muscle-derived interleukin-6. Physiol. Rev. 2008, 88, 1379–1406. [Google Scholar] [CrossRef]
- Qureshi, I.Z.; Ambreen, F. Serum APOE, leptin, CFH and HTRA1 levels in Pakistani age related macular degeneration patients. J. Pak. Med. Assoc. 2017, 67, 852–857. [Google Scholar]
- Gesuita, R.; Licini, C.; Picchiassi, E.; Tarquini, F.; Coata, G.; Fantone, S.; Tossetta, G.; Ciavattini, A.; Castellucci, M.; Di Renzo, G.C.; et al. Association between first trimester plasma htra1 level and subsequent preeclampsia: A possible early marker? Pregnancy Hypertens. 2019, 18, 58–62. [Google Scholar] [CrossRef]
- Supanji; Shimomachi, M.; Hasan, M.Z.; Kawaichi, M.; Oka, C. HtrA1 is induced by oxidative stress and enhances cell senescence through p38 MAPK pathway. Exp. Eye Res. 2013, 112, 79–92. [Google Scholar] [CrossRef]
- Wang, L.; Huang, Y.; Wang, X.; Chen, Y. Label-Free LC-MS/MS Proteomics Analyses Reveal Proteomic Changes Accompanying MSTN KO in C2C12 Cells. Biomed. Res. Int. 2019, 2019, 7052456. [Google Scholar] [CrossRef]
- Tai, Y.K.; Chan, K.K.W.; Fong, C.H.H.; Ramanan, S.; Yap, J.L.Y.; Yin, J.N.; Yip, Y.S.; Tan, W.R.; Koh, A.P.F.; Tan, N.S.; et al. Modulated TRPC1 Expression Predicts Sensitivity of Breast Cancer to Doxorubicin and Magnetic Field Therapy: Segue Towards a Precision Medicine Approach. Front. Oncol. 2021, 11, 783803. [Google Scholar] [CrossRef]
- Chen, N.; Ritsma, L.M.A.; Vrisekoop, N. In vivo characteristics of human and mouse breast tumor cell lines. Exp. Cell Res. 2019, 381, 86–93. [Google Scholar] [CrossRef]
- Chu, P.Y.; Koh, A.P.; Antony, J.; Huang, R.Y. Applications of the Chick Chorioallantoic Membrane as an Alternative Model for Cancer Studies. Cells Tissues Organs 2021, 211, 222–237. [Google Scholar] [CrossRef]
- Langley, B.; Thomas, M.; Bishop, A.; Sharma, M.; Gilmour, S.; Kambadur, R. Myostatin inhibits myoblast differentiation by down-regulating MyoD expression. J. Biol. Chem. 2002, 277, 49831–49840. [Google Scholar] [CrossRef]
- Pedersen, B.K. Exercise-induced myokines and their role in chronic diseases. Brain Behav. Immun. 2011, 25, 811–816. [Google Scholar] [CrossRef]
- Savci-Heijink, C.D.; Halfwerk, H.; Hooijer, G.K.J.; Koster, J.; Horlings, H.M.; Meijer, S.L.; van de Vijver, M.J. Epithelial-to-mesenchymal transition status of primary breast carcinomas and its correlation with metastatic behavior. Breast Cancer Res. Treat. 2019, 174, 649–659. [Google Scholar] [CrossRef]
- Ristow, M.; Schmeisser, K. Mitohormesis: Promoting Health and Lifespan by Increased Levels of Reactive Oxygen Species (ROS). Dose Response 2014, 12, 288–341. [Google Scholar] [CrossRef]
- Jee, H.; Park, E.; Hur, K.; Kang, M.; Kim, Y. High-Intensity Aerobic Exercise Suppresses Cancer Growth by Regulating Skeletal Muscle-Derived Oncogenes and Tumor Suppressors. Front. Mol. Biosci. 2022, 9, 818470. [Google Scholar] [CrossRef]
- Cerqueira, E.; Marinho, D.A.; Neiva, H.P.; Lourenco, O. Inflammatory Effects of High and Moderate Intensity Exercise-A Systematic Review. Front. Physiol. 2019, 10, 1550. [Google Scholar] [CrossRef]
- Klose, R.; Adam, M.G.; Weis, E.M.; Moll, I.; Wustehube-Lausch, J.; Tetzlaff, F.; Oka, C.; Ehrmann, M.; Fischer, A. Inactivation of the serine protease HTRA1 inhibits tumor growth by deregulating angiogenesis. Oncogene 2018, 37, 4260–4272. [Google Scholar] [CrossRef]
- Yang, W.; Huang, J.; Wu, H.; Wang, Y.; Du, Z.; Ling, Y.; Wang, W.; Wu, Q.; Gao, W. Molecular mechanisms of cancer cachexia-induced muscle atrophy (Review). Mol. Med. Rep. 2020, 22, 4967–4980. [Google Scholar] [CrossRef]
- Petrosino, J.M.; Heiss, V.J.; Maurya, S.K.; Kalyanasundaram, A.; Periasamy, M.; LaFountain, R.A.; Wilson, J.M.; Simonetti, O.P.; Ziouzenkova, O. Graded Maximal Exercise Testing to Assess Mouse Cardio-Metabolic Phenotypes. PLoS ONE 2016, 11, e0148010. [Google Scholar] [CrossRef]
Antibody Name | Dilution Factor | Cat. No. | Manufacturer |
---|---|---|---|
HTRA1 | 1:1000 | #55011-1-AP | Proteintech |
MyoD | 1:300 | #sc-71629 | Santa Cruz |
Myogenin | 1:300 | #sc-12732 | Santa Cruz |
p21 | 1:300 | #sc-6246 | Santa Cruz |
Desmin | 1:300 | #ab907 | Merck |
GAPDH | 1:10,000 | #60004-1-1g | Proteintech |
α-tubulin | 1:10,000 | #66031-1-1g | Proteintech |
β-actin | 1:10,000 | #60008-1-1g | Proteintech |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
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
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 StyleTai, 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