Melder R J, Salehi H A, Jain R K
Edwin L. Steele Laboratory, Department of Radiation Oncology, Harvard Medical School, Boston, Massachusetts, USA.
Microvasc Res. 1995 Jul;50(1):35-44. doi: 10.1006/mvre.1995.1036.
A mammary carcinoma, MCa IV, was grown in syngeneic C3H mice in a cranial window preparation which permitted the in vivo observation of the growth and microcirculation of the tumors. Fluorescently labeled activated natural killer (A-NK) cells were injected into the external carotid artery and their interactions with normal and tumor vessels were quantified by video microscopy. Cells which entered the tumor vessels adhered heterogeneously to these vessels, regardless of vessel size or blood flow rates and bound with an efficiency ranging from 0 to 82% of the incoming cell flux. Normal brain tissue showed significantly fewer binding cells per microscopic field (9 +/- 5 vs 85 +/- 27 cells/1.3 mm2) and the few cells which were retained by the normal tissue were highly deformed, suggesting mechanical rather than adhesive entrapment. These studies indicate that A-NK cells bind in high numbers to segments of the vessels of mammary tumors growing in an intracranial site when administered through an arterial route; however, some tumor vessels may escape recognition by these cells. These findings suggest that A-NK cells may be used as carriers of genes for anti-cancer agents.
将一株IV期乳腺癌(MCa IV)种植于同基因C3H小鼠的颅窗标本中,以便在体内观察肿瘤的生长及微循环情况。将荧光标记的活化自然杀伤(A-NK)细胞注入颈外动脉,并通过视频显微镜对其与正常血管及肿瘤血管的相互作用进行定量分析。进入肿瘤血管的细胞会以异质性方式黏附于这些血管,而与血管大小或血流速度无关,黏附效率在进入细胞通量的0%至82%之间。正常脑组织每个显微镜视野中的黏附细胞明显较少(9±5个对85±27个细胞/1.3平方毫米),且正常组织中留存的少数细胞高度变形,提示为机械性而非黏附性截留。这些研究表明,经动脉途径给药时,A-NK细胞会大量黏附于颅内生长的乳腺肿瘤血管段;然而,一些肿瘤血管可能会逃避这些细胞的识别。这些发现提示,A-NK细胞可用作抗癌药物基因的载体。