Coomber B L, Stewart P A, Hayakawa E M, Farrell C L, Del Maestro R F
Department of Anatomy, University of Toronto, Ontario, Canada.
J Neuropathol Exp Neurol. 1988 Jan;47(1):29-40. doi: 10.1097/00005072-198801000-00004.
Normal blood vessels invading a growing neoplasm undergo dramatic changes in morphology. Whether vessel characteristics are dictated entirely by the tumor, or from developmental restrictions in normal vessels from which tumor vessels originate is not known. To address this question we challenged two morphologically different types of capillaries (brain and muscle) with the same tumor environment (C6 astrocytoma), and quantified the invading vessel morphology. A vascular spheroids of C6 astrocytoma cells were implanted singly into rat cerebral cortex or iliacus muscle. Microvessels from the tumor, peritumoral tissue and control tissue were examined ultrastructurally and quantified. Tumor vessels differed significantly from host vessels but not from each other, regardless of implantation site. Neoplastic vessels were thick-walled relative to normal host vessels, had low densities of mitochondria and vesicular structures, and had both fenestrations and enlarged junctional clefts characteristic of highly permeable vessels. Control brain vessels were typically thin-walled, had a high density of mitochondria, a low density of endothelial vesicles and continuous tight junctions. Control muscle vessels were thin-walled with a low density of mitochondria, high density of vesicles and junctional zones with occasional enlarged clefts. Peritumoral vessel morphology was intermediate between that of tumor and the corresponding control tissue. We propose that C6 astrocytoma cells influence invading endothelial cells to develop a permeable phenotype radically different from host tissue endothelium, and host vessel phenotype does not influence tumor vessel morphology.
侵入生长中的肿瘤的正常血管会发生显著的形态变化。血管特征是完全由肿瘤决定，还是由肿瘤血管起源的正常血管的发育限制所决定，目前尚不清楚。为了解决这个问题，我们用相同的肿瘤环境（C6星形细胞瘤）对两种形态不同的毛细血管（脑毛细血管和肌肉毛细血管）进行了挑战，并对侵入血管的形态进行了量化。将单个C6星形细胞瘤细胞的血管球植入大鼠大脑皮层或髂肌。对肿瘤、肿瘤周围组织和对照组织的微血管进行超微结构检查并量化。无论植入部位如何，肿瘤血管与宿主血管有显著差异，但彼此之间无差异。相对于正常宿主血管，肿瘤血管壁增厚，线粒体和囊泡结构密度低，具有窗孔和高度通透性血管特有的扩大连接间隙。对照脑毛细血管通常壁薄，线粒体密度高，内皮囊泡密度低，紧密连接连续。对照肌肉血管壁薄，线粒体密度低，囊泡密度高，连接区偶尔有扩大的间隙。肿瘤周围血管形态介于肿瘤和相应对照组织之间。我们认为，C6星形细胞瘤细胞影响侵入的内皮细胞形成一种与宿主组织内皮截然不同的通透性表型，而宿主血管表型不影响肿瘤血管形态。
