Unveiling the role of tumor reactive stroma in cholangiocarcinoma: an opportunity for new therapeutic strategies.
Unveiling the role of tumor reactive stroma in cholangiocarcinoma: an opportunity for new therapeutic strategies.
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DOI：
10.3978/j.issn.2224-4778.2013.04.02
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发表时间：
2013-07
期刊：
影响因子：
--
通讯作者：
Fabris L
中科院分区：
文献类型：
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作者：
Cadamuro M;Morton SD;Strazzabosco M;Fabris L
胆管细胞癌(CCA)是一种侵袭性很强的肿瘤，其发病率在过去十年中呈稳步上升趋势。尽管它的流行病学影响越来越大，但具有治愈意图的治疗机会仍然局限于手术切除，在高度挑选的病例中，还限于肝移植。不幸的是，在大多数确诊时，CCA已经转移到区域淋巴结，从而减少了根治性治疗的机会。管理CCA侵入性的机制尚不清楚。CCA的一个关键成分是丰富的“肿瘤反应性间质”，它与肿瘤的生长密切相关。大量的反应性间质存在于许多具有强侵袭性特征的癌症中，即胃癌、结直肠癌和胰腺癌，以及乳腺癌。在肿瘤间质中，各种信号和介质在间质和癌细胞之间相互交换，进而获得促侵袭特性。这些旁分泌通讯直到最近才开始被阐明，可能代表了特定治疗干预的靶点。在这篇综述中，我们将重点介绍CCA中组成肿瘤反应性间质的细胞类型，以及可能导致CCA侵袭性增加的一些分子相互作用。还将描述解剖这些相互作用的可能性，以及可能利用这些相互作用进行潜在的新治疗。
Cholangiocarcinoma (CCA) is a very aggressive neoplasm, whose incidence has steadily increased in the last decade. Despite its growing epidemiological impact, therapeutic chances with a curative intent are still limited to surgical resection and, in highly selected cases, to liver transplantation. Unfortunately, in most cases at the time of diagnosis, CCA has already metastasized to regional lymph nodes, thereby reducing the opportunities for curative treatment. Mechanisms governing CCA invasiveness are unclear. A critical element of CCA is the abundant “tumor reactive stroma”, which develops in close association with tumor growth. An abundant reactive stroma is present in a number of carcinomas characterized by strong invasiveness, namely gastric, colorectal and pancreatic cancers, as well as breast cancer. In tumor stroma, a variety of signals and mediators are reciprocally exchanged between stromal and cancer cells that, in turn acquire pro-invasive properties. These paracrine communications have started to be elucidated only recently, and may represent targets amenable of specific therapeutic intervention. In this review, we will highlight the cell types that compose the tumor reactive stroma in CCA and some of the molecular interactions possibly responsible for increased invasiveness of CCA. The possibility of dissecting, and likely exploiting, these interactions for potential new treatments will be also described.