Cancer and Immunogenetics Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
Br J Cancer. 2013 May 28;108(10):2106-15. doi: 10.1038/bjc.2013.209. Epub 2013 May 7.
Myofibroblasts have an important role in regulating the normal colorectal stem cell niche. While the activation of myofibroblasts in primary colorectal cancers has been previously described, myofibroblast activation in lymph node metastases has not been described before.
Paraffin-embedded lymph node sections from patients with macrometastases, micrometastases and isolated tumour cells were stained to identify myofibroblasts and to characterise the distribution of different cell types in tumour-containing lymph nodes. The extent of myofibroblast presence was quantified and compared with the size of the metastasis and degree of proliferation and differentiation of the cancer cells.
We show substantial activation of myofibroblasts in the presence of colorectal metastases in lymph nodes, which is intimately associated with glandular structures, both in micro- and macrometastases. The degree of activation is positively associated with the size of the metastases and the proportion of Ki67+ve cancer cells, and negatively associated with the degree of enterocyte differentiation as measured by CK20 expression.
The substantial activation of myofibroblasts in tumour-containing lymph nodes strongly suggests that these metastatic cancer cells are still significantly dependent on their microenvironment. Further understanding of these epithelial-mesenchymal interactions could lead to the development of new therapies in metastatic disease.
肌成纤维细胞在调节正常结直肠干细胞龛中起着重要作用。虽然以前已经描述了原发性结直肠癌中肌成纤维细胞的激活,但以前尚未描述淋巴结转移中肌成纤维细胞的激活。
对来自有大转移、微转移和孤立肿瘤细胞的患者的石蜡包埋淋巴结切片进行染色,以鉴定肌成纤维细胞,并描绘肿瘤内淋巴结中不同细胞类型的分布。定量评估肌成纤维细胞的存在程度,并将其与转移的大小以及癌细胞的增殖和分化程度进行比较。
我们在微转移和大转移中均发现,存在结直肠转移时肌成纤维细胞大量激活,且与腺结构密切相关。激活程度与转移的大小以及 Ki67+ve 癌细胞的比例呈正相关,与 CK20 表达测量的肠细胞分化程度呈负相关。
富含肿瘤的淋巴结中肌成纤维细胞的大量激活强烈表明,这些转移性癌细胞仍然严重依赖于其微环境。进一步了解这些上皮-间充质相互作用可能会导致转移性疾病新疗法的发展。