Onset of abnormal blood and lymphatic vessel function and interstitial hypertension in early stages of carcinogenesis
Onset of abnormal blood and lymphatic vessel function and interstitial hypertension in early stages of carcinogenesis
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DOI：
10.1158/0008-5472.can-05-2655
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发表时间：
2006-04-01
期刊：
影响因子：
11.2
通讯作者：
Jain, RK
中科院分区：
文献类型：
--
作者：
Hagendoorn, J;Tong, R;Jain, RK
诊断方法的最新改进为在早期阶段检测和治疗（前）恶性病变开辟了途径。然而，由于缺乏既能模拟人类致癌作用又能对血管系统进行直接光学成像的自发性肿瘤模型，人们对癌症发展早期阶段血管和淋巴管的功能知之甚少。在这里，我们在DNTA聚合酶eta缺陷小鼠的皮肤中使用了自发性癌变模型，发现在增生/发育不良阶段，间质液压力已经升高。这伴随着血管生成的血管系统，表现出改变的渗透性，血管压缩，并减少α-平滑肌肌动蛋白阳性血管周围细胞覆盖。此外，增生/异型增生病变中的淋巴管部分受压且无功能。这些新的见解可能有助于癌症的早期检测和治疗策略。
Recent improvements in diagnostic methods have opened avenues for detection and treatment of (pre)malignant lesions at early stages. However, due to the lack of spontaneous tumor models that both mimic human carcinogenesis and allow direct optical imaging of the vasculature, little is known about the function of blood and lymphatic vessels during the early stages of cancer development. Here, we used a spontaneous carcinogenesis model in the skin of DNTA polymerase eta-deficient mice and found that interstitial fluid pressure was already elevated in the hyperplastic/dysplastic stage. This was accompanied by angiogenic blood vasculature that exhibited altered permeability, vessel compression, and decreased alpha-smooth muscle actin-positive perivascular cell coverage. In addition, the lymphatic vessels in hyperplastic/dysplastic lesions were partly compressed and nonfunctional. These novel insights may aid early detection and treatment strategies for cancer.