Laboratory of Experimental Surgery, Department of Human Structure and Repair, Ghent University, Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent University, Ghent, Belgium.
Department of Pathology, Ghent University Hospital, Ghent, Belgium.
Exp Mol Pathol. 2020 Aug;115:104442. doi: 10.1016/j.yexmp.2020.104442. Epub 2020 Apr 17.
Recent insights have implicated mesothelial-to-mesenchymal transition (MMT) as a mechanism by which mesothelial cells can transdifferentiate into cancer-associated fibroblasts (CAFs) in several cancers metastasizing to the peritoneum. However, this was not evaluated extensively in colorectal cancer. We examined the presumed mesothelial origin of CAFs in three types of colorectal carcinoma: conventional type adenocarcinoma, mucinous carcinoma and signet ring cell carcinoma. We evaluated the expression of mesothelial, mesenchymal, angiogenesis and colorectal cancer-related markers in peritoneal samples of twelve colorectal cancer patients with peritoneal carcinomatosis and four control patients by immunohistochemistry. We observed morphological and immunohistochemical changes in the vicinity of tumor implants in all studied colorectal cancer types. Mesothelial cells acquired a spindle-shaped myofibroblast-like morphology, lost expression of mesothelial markers, and gained expression of mesenchymal markers. Analysis of consecutive tissue sections and double staining for mesothelial and mesenchymal markers revealed overlap in expression of mesothelial and CAF markers. These findings are highly suggestive of a mesothelial origin of CAFs in peritoneal carcinomatosis in colorectal cancer. Interfering with the process of MMT might be a valuable approach in treating and preventing peritoneal carcinomatosis. Differences observed between colorectal cancer types suggest that one single strategy might not be applicable.
最近的研究表明，间皮细胞向间充质转化（MMT）是一种机制，通过这种机制，间皮细胞可以在几种转移到腹膜的癌症中向癌相关成纤维细胞（CAF）转分化。然而，这在结直肠癌中并没有得到广泛评估。我们检查了三种类型的结直肠癌中 CAF 的假定间皮起源：常规型腺癌、黏液腺癌和印戒细胞癌。我们通过免疫组织化学评估了 12 例腹膜转移结直肠癌患者和 4 例对照患者腹膜样本中 12 例结直肠癌患者的间皮、间充质、血管生成和结直肠癌相关标志物的表达。我们观察了所有研究的结直肠癌类型中肿瘤植入物附近的形态和免疫组织化学变化。间皮细胞获得了纺锤形成纤维细胞样形态，丧失了间皮标志物的表达，获得了间充质标志物的表达。对连续组织切片的分析和间皮和间充质标志物的双重染色显示，间皮和 CAF 标志物的表达有重叠。这些发现高度提示结直肠癌腹膜转移中的 CAF 来源于间皮。干扰 MMT 过程可能是治疗和预防腹膜转移的一种有价值的方法。观察到的结直肠癌类型之间的差异表明，一种单一的策略可能不适用。
