Laboratory of Biochemistry and Experimental Morphology, CIAFEL, Porto, Portugal.
Department of Physical Medicine and Rehabilitation, Hospital-Escola, Fernando Pessoa University, Gondomar, Portugal.
Int J Sports Med. 2021 May;42(5):389-406. doi: 10.1055/a-1308-3476. Epub 2020 Dec 11.
The tumor vessel network has been investigated as a precursor of an inhospitable tumor microenvironment, including its repercussions in tumor perfusion, oxygenation, interstitial fluid pressure, pH, and immune response. Dysfunctional tumor vasculature leads to the extravasation of blood to the interstitial space, hindering proper perfusion and causing interstitial hypertension. Consequently, the inadequate delivery of oxygen and clearance of by-products of metabolism promote the development of intratumoral hypoxia and acidification, hampering the action of immune cells and resulting in more aggressive tumors. Thus, pharmacological strategies targeting tumor vasculature were developed, but the overall outcome was not satisfactory due to its transient nature and the higher risk of hypoxia and metastasis. Therefore, physical exercise emerged as a potential favorable modulator of tumor vasculature, improving intratumoral vascularization and perfusion. Indeed, it seems that regular exercise practice is associated with lasting tumor vascular maturity, reduced vascular resistance, and increased vascular conductance. Higher vascular conductance reduces intratumoral hypoxia and increases the accessibility of circulating immune cells to the tumor milieu, inhibiting tumor development and improving cancer treatment. The present paper describes the implications of abnormal vasculature on the tumor microenvironment and the underlying mechanisms promoted by regular physical exercise for the re-establishment of more physiological tumor vasculature.
肿瘤血管网络被研究为不利于肿瘤微环境的前兆，包括其对肿瘤灌注、氧合、细胞外间质压力、pH 值和免疫反应的影响。功能失调的肿瘤血管导致血液渗出到细胞外间质，阻碍适当的灌注并导致细胞外间质高压。因此，氧气输送不足和代谢产物的清除会促进肿瘤内缺氧和酸化，抑制免疫细胞的作用，并导致更具侵袭性的肿瘤。因此，开发了针对肿瘤血管的药理学策略，但由于其短暂性和更高的缺氧和转移风险，总体效果并不理想。因此，体育锻炼作为肿瘤血管的一种潜在有利调节剂出现，改善了肿瘤内血管生成和灌注。事实上，经常锻炼似乎与肿瘤血管的持久成熟、血管阻力降低和血管传导性增加有关。较高的血管传导性可降低肿瘤内缺氧程度，增加循环免疫细胞进入肿瘤环境的可及性，从而抑制肿瘤发展并改善癌症治疗效果。本文描述了异常血管对肿瘤微环境的影响，以及经常进行体育锻炼为重建更具生理功能的肿瘤血管所促进的潜在机制。
