Vascular channel formation by human melanoma cells in vivo and in vitro:: Vasculogenic mimicry
Vascular channel formation by human melanoma cells in vivo and in vitro:: Vasculogenic mimicry
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DOI：
10.1016/s0002-9440(10)65173-5
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发表时间：
1999-09-01
影响因子：
6
通讯作者：
Hendrix, MJC
中科院分区：
文献类型：
--
作者：
Maniotis, AJ;Folberg, R;Hendrix, MJC
侵袭性人眼内（葡萄膜）和转移性皮肤黑色素瘤的组织切片通常缺乏明显坏死的证据，并含有细胞外基质互连环的图案化网络。形成这些环或网络的基质可以是实心的或中空的。在组织学上，已在该图案化基质的中空通道组分内检测到红细胞，并且已在人类肿瘤中通过血管造影检测到这些血管通道网络。通过光学显微镜、透射电子显微镜或通过使用内皮细胞标记物的免疫组织化学组，在这些基质包埋的通道内未鉴定出内皮细胞（因子VIII相关抗原、Ulex、CD 31、CD 34和KDR[Flk-1]）。高度侵袭性的原发性和转移性人黑色素瘤细胞在含有Matrigel或稀释的I型胶原蛋白的三维培养物中形成图案化的实心和中空基质通道（在侵袭性原发性和转移性人黑色素瘤的组织切片中可见），而没有内皮细胞或成纤维细胞。这些肿瘤细胞产生的图案化通道传导染料，突出显示了人类肿瘤中血管造影可视化的环状图案。在相同的培养条件下，正常黑素细胞和侵袭性差的黑色素瘤细胞都不能在体外产生这些图案化通道，即使在加入来自转移性图案形成黑色素瘤细胞的条件培养基、可溶性生长因子或缺氧方案之后，高度侵袭性和转移性的人黑色素瘤细胞，但使侵袭性差的黑色素瘤细胞凝结，收缩和重塑漂浮的水合凝胶，为体外微血管的生成提供了生物力学解释。高侵袭性与低侵袭性黑色素瘤肿瘤细胞的cDNA微阵列分析证实了在高侵袭性黑色素瘤细胞中向多能胚胎样基因型的遗传逆转。这些观察结果强烈表明，侵袭性黑色素瘤细胞可能产生血管通道，促进肿瘤灌注独立于肿瘤血管生成。
Tissue sections from aggressive human intraocular (uveal) and metastatic cutaneous melanomas generally lack evidence of significant necrosis and contain patterned networks of interconnected loops of extracellular matrix. The matrix that forms these loops or networks may be solid or hollow. Red blood cells have been detected within the hollow channel components of this patterned matrix histologically, and these vascular channel networks have been detected in human tumors angiographically, Endothelial cells were not identified within these matrix-embedded channels by light microscopy, by transmission electron microscopy, or by using an immunohistochemical panel of endothelial cell markers (Factor VIII-related antigen, Ulex, CD31, CD34, and KDR[Flk-1]). Highly invasive primary and metastatic human melanoma cells formed patterned solid and hollow matrix channels (seen in tissue sections of aggressive primary and metastatic human melanomas) in three-dimensional cultures containing Matrigel or dilute Type I collagen, without endothelial cells or fibroblasts. These tumor cell-generated patterned channels conducted dye, highlighting looping patterns visualized angiographically in human tumors. Neither normal melanocytes nor poorly invasive melanoma cells generated these patterned channels in vitro under identical culture conditions, even after the addition of conditioned medium from metastatic pattern-forming melanoma cells, soluble growth factors, or regimes of hypoxia, Highly invasive and metastatic human melanoma cells, but clot poorly invasive melanoma cells, contracted and remodeled floating hydrated gels, providing a biomechanical explanation for the generation of microvessels in vitro. cDNA microarray analysis of highly invasive versus poorly invasive melanoma tumor cells confirmed a genetic reversion to a pluripotent embryonic-like genotype in the highly aggressive melanoma cells. These observations strongly suggest that aggressive melanoma cells may generate vascular channels that facilitate tumor perfusion independent of tumor angiogenesis.