Department of Surgery, Section of Urology MC6038, The University of Chicago, Chicago, IL 60637, USA.
Clin Exp Metastasis. 2010 Mar;27(3):185-96. doi: 10.1007/s10585-010-9317-0. Epub 2010 Mar 14.
Despite the potentially crucial contributions of the omentum in the regulation of ovarian cancer metastatic growth, it remains a poorly understood organ. Due to its anatomic location and structural fragility, the omentum presents inherent challenges to mechanism-based in vivo studies. Thus, the availability of an ex vivo omental model would, in part, address some of these difficulties posed. Here we describe a technique for identifying, isolating and maintaining ex vivo cultures of omenta from immune-compromised and -competent mice. Ex vivo culture conditions were developed that maintain tissue viability, architecture, and function for up to 10 days. Further experiments demonstrate that the ex vivo culture conditions allow for the proliferation of ovarian cancer cells in vitro and support a similar pattern of microscopic lesions after either intraperitoneal injection of ovarian cancer cells or co-culture of ovarian cancer cells with the omentum. In agreement with previous studies from our laboratory, histologic evaluation of these specimens found that ovarian cancer cells, as well as other peritoneal cancer cells, preferentially accumulate in, and colonize, omental areas rich in immune cells. We now recognize that these are specific, functional structures referred to as milky spots. In sum, these are foundational studies of a readily accessible model, which is easily manipulated and can be immediately used to study the dynamic process of omental colonization. It is hoped that investigators will use the data herein as a starting point for refinements and modifications which will enable them to tailor the model to the specific needs of the experimental question(s) they wish to pursue.
尽管网膜在调节卵巢癌转移生长方面可能具有至关重要的作用,但它仍然是一个尚未被充分了解的器官。由于其解剖位置和结构脆弱性,网膜在基于机制的体内研究中存在固有挑战。因此,外生网膜模型的可用性将在一定程度上解决这些困难。在这里,我们描述了一种从免疫功能正常和免疫功能低下的小鼠中识别、分离和维持外生网膜培养物的技术。我们开发了外生培养条件,可维持组织活力、结构和功能长达 10 天。进一步的实验表明,外生培养条件允许卵巢癌细胞在体外增殖,并在卵巢癌细胞腹腔内注射或与网膜共培养后支持类似的微观病变模式。与我们实验室之前的研究一致,对这些标本的组织学评估发现,卵巢癌细胞以及其他腹膜癌细胞优先在富含免疫细胞的网膜区域中积累和定植。我们现在认识到,这些是称为乳斑的特定功能结构。总之,这些是易于获取的模型的基础研究,易于操作,可立即用于研究网膜定植的动态过程。希望研究人员将本文中的数据作为起点,进行改进和修改,使他们能够根据自己希望研究的具体实验问题的需求来调整模型。