Tumor-Derived Exosomes Promote Tumor Growth Through Modulating Microvascular Hemodynamics in a Human Ovarian Cancer Xenograft Model

IF 1.9 4区医学 Q3 HEMATOLOGY

Microcirculation Pub Date : 2024-07-15 DOI:10.1111/micc.12876

Qin Wang, Xiaoyan Zhang, Bingwei Li, Xueting Liu, Ailing Li, Hongwei Li, Xiaohua Shi, Jianqun Han

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引用次数: 0

Abstract

Objective

Abnormal tumor vascular network contributes to aberrant blood perfusion and reduced oxygenation in tumors, which lead to poor efficacy of chemotherapy and radiotherapy. We aimed to explore the effects of the tumor-derived exosomes (TDEs) and C188-9 (a small molecule inhibitor of signal transducer and activator of transcription 3, STAT3) on tumor microvascular hemodynamics and determine which blood flow oscillations for various frequency intervals are responsible for these changes.

Methods

Microvascular hemodynamics parameters were recorded using a PeriFlux 6000 EPOS system in tumor surface in a nude mouse subcutaneous xenograft model. Oscillations of laser Doppler flowmetry (LDF) signal were investigated by wavelet transform analysis.

Results

TDEs facilitated tumor growth at least partially was associated with increasing blood flow in smaller vessels with lower speed and decreasing the blood flow at larger vessels with higher speed. Lower oxyhemoglobin saturation (SO₂) on tumor surface was aggravated by TDEs, and C188-9 treatment significantly alleviated this decrease. Wavelet transform spectral analysis revealed that TDEs increased the amplitude of oscillations in four frequency intervals related to endothelial (NO-dependent and -independent), myogenic and neurogenic activities, and C188-9 had no effect on this increase.

Conclusions

TDEs facilitated tumor growth partially was associated with increasing blood flow in distributing vessels, reducing blood perfusion in larger vessels, and lowering SO₂ on tumor surface. Enhanced vascular smooth muscle, endothelial and neurogenic activities occurred in tumor superficial zone.

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肿瘤外泌体通过调节人卵巢癌异种移植模型中的微血管血流动力学促进肿瘤生长

目的：肿瘤血管网络异常会导致肿瘤血液灌注异常和氧含量降低，从而导致化疗和放疗疗效不佳。我们旨在探索肿瘤外泌体（TDEs）和 C188-9（一种信号转导子和转录激活子 3 STAT3 的小分子抑制剂）对肿瘤微血管血流动力学的影响，并确定不同频率间隔的血流振荡是造成这些变化的原因：方法：使用 PeriFlux 6000 EPOS 系统记录裸鼠皮下异种移植模型肿瘤表面的微血管血流动力学参数。通过小波变换分析研究了激光多普勒血流测量仪（LDF）信号的振荡：结果：TDEs 至少在一定程度上促进了肿瘤的生长，这与流速较低的小血管血流增加和流速较高的大血管血流减少有关。TDEs 加剧了肿瘤表面氧合血红蛋白饱和度（SO2）的降低，而 C188-9 治疗显著缓解了这种降低。小波变换频谱分析表明，TDEs 增加了与内皮（NO 依赖性和非依赖性）、肌源和神经源活动有关的四个频率区间的振荡幅度，而 C188-9 对这种增加没有影响：TDEs促进肿瘤生长的部分原因与增加分布血管的血流量、减少较大血管的血液灌注和降低肿瘤表面的二氧化硫有关。肿瘤浅表区的血管平滑肌、内皮细胞和神经原活动增强。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Microcirculation 医学-外周血管病

CiteScore

5.00

自引率

4.20%

发文量

审稿时长

6-12 weeks

期刊介绍： The journal features original contributions that are the result of investigations contributing significant new information relating to the vascular and lymphatic microcirculation addressed at the intact animal, organ, cellular, or molecular level. Papers describe applications of the methods of physiology, biophysics, bioengineering, genetics, cell biology, biochemistry, and molecular biology to problems in microcirculation. Microcirculation also publishes state-of-the-art reviews that address frontier areas or new advances in technology in the fields of microcirculatory disease and function. Specific areas of interest include: Angiogenesis, growth and remodeling; Transport and exchange of gasses and solutes; Rheology and biorheology; Endothelial cell biology and metabolism; Interactions between endothelium, smooth muscle, parenchymal cells, leukocytes and platelets; Regulation of vasomotor tone; and Microvascular structures, imaging and morphometry. Papers also describe innovations in experimental techniques and instrumentation for studying all aspects of microcirculatory structure and function.