Mechanical load inhibition of heart tumours: Is it also true for skeletal and smooth muscle?

While reading an interesting article published in Science (1), I wondered whether mechanical load alongside its related nesprin 2 overexpression could also play a role in the inhibition of benign and malignant tumours originating from skeletal and smooth muscle tissues within various body sites.
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Indeed, although skeletal and smooth musculature are being kept repeatedly active from a mechanical standpoint, rhabdomyosarcomas account for more than half of all soft tissue sarcomas in children (2), while uterine leiomiomas are frequently observed in female patients (3).

Based upon the above, I think it would make sense to characterize nesprin 2 expression within the aforementioned tumours, respectively affecting pediatric and adult individuals. As a matter of fact, this could provide further support to the putative role played by mechanical load-induced nesprin 2 expression as an inhibitor of neoplastic transformation at cardiac level (1).

Within this challenging and scientifically intriguing context, the potential contribution of hypoxia and micro-nanoplastics (MNPs) to heart tumour development should not be neglected. More in detail, hypoxic signaling pathways have been reported to play a significant role in the aetio-pathogenesis of carotid body glomic neoplasms (4), alias chemodectomas, with two similar chemoreceptors, namely the aortic and pulmonary ones, being located within the heart district. Furthermore, a tissue hypoxic microenvironment, typically experienced by people living at very high altitudes, has been clearly shown to induce an increased biosynthesis and release of hypoxia-inducible factor-1 (HIF-1), a key infiammatory mediator (4), with chronic infiammation having been also reported to play  a crucial role in carcinogenesis (5).

As far as MNPs are specifically concerned, the widespread contamination brought by them to global seas and oceans is a matter of serious concern (6). Noteworthy, the well-established capability of MNPs to travel via the haematogenous route throughout the bodies of exposed humans and animals allows them to potentially reach any host's tissue - including the brain and the heart -, with polystyrene nanoplastic-induced cardiotoxicity having been recently described (7). Additionally, the proven ability of MNPs to attract and concentrate several protozoan and viral pathogens alongside antibiotic-resistant bacteria and a huge number of persistent environmental pollutants (8), including the oncogenic PAHs and PFAS "forever chemicals", should be carefully assessed in relation to heart tumor development.

As a concluding remark, all the aforementioned hypotheses and considerations could be of significant value also from a comparative pathology and translational medicine perspective, thus being in full agreement with the "One Health" concept, reminding us that human, animal, and environmental health are mutually and tightly linked to each other.

References 

1) Ciucci G, Lorizio D, Bartoloni N, Budini M, Colliva A, Vodret S, Nguyen AV, Ciacci L, Texler B, Cardini B, Oberhuber R, Bindelli S, Del Giudice ILC, Vuerich R, Riccitelli F, Zago E, Finsberg HN, Chiesa M, Perrucci GL, Bussani R, Silvestri F, Maglione M, Dellino GI, Sinagra G, Giacca M, Eschenhagen T, Golino P, Pompilio G, Pelicci PG, Andolfi L, Pinamonti M, Dal Ferro M, Wall S, Loffredo FS, Zacchigna S. Mechanical load inhibits cancer growth in mouse and human hearts. Science 2026;392(6796):eads9412. 

DOI:10.1126/science.ads9412.

2) Arndt CAS, Crist WM. Common musculoskeletal tumors of childhood and adolescence. N. Engl. J. Med. 1999;341:342-352.

DOI: 10.1056/NEJM199907293410507.

 

3) Lewis TD, Malik M, Britten J, San Pablo AM, Catherino WH. A Comprehensive Review of the Pharmacologic Management of Uterine Leiomyoma. Biomed. Res. Int. 2018;2414609. 

DOI: 10.1155/2018/2414609.

 

4) Cao K, Yuan W, Hou C, Wang Z, Yu J, Wang T. Hypoxic Signaling Pathways in Carotid Body Tumors. Cancers (Basel). 2024 Jan 30;16(3):584. 

DOI:10.3390/cancers16030584.

5) Ma S, Zhang Y, Fan Z, He F, Li X, Chen R, Wang S, Wei W. Impact of a pro-inflammatory diet on upper gastrointestinal cancer risk: evidence from a population-based cohort in high-risk areas of China. Eur. J. Nutr. 2026; 65(4):127. 
DOI:10.1007/s00394-026-03970-4.
 
 
6) Di Guardo G. Micro-nanoplastics: a serious threat to whales' health and conservation. BMJ 2024;386:q2095.
DOI:10.1136/bmj.q2095. 
 
 
7).Kang H, Huang D, Zhang W, Wang J, Liu Z, Wang Z, Jiang G, Gao A. Propionic acid/FBP1 is involved in polystyrene nanoplastic-induced cardiac injury via the gut-heart axis. Part. Fibre Toxicol. 2025;22(1):10. 
DOI:10.1186/s12989-025-00626-9.
 
8) Di Guardo G. Flood-Associated, Land-to-Sea Pathogens' Transfer: A One Health Perspective. Pathogens 2023;12(11):1348. 
DOI:10.3390/pathogens12111348. 



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