The role of the peritoneal microenvironment in the pathogenesis of colorectal peritoneal carcinomatosis.

Abstract:

: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.

journal_name

Exp Mol Pathol

authors

Demuytere J,Ceelen W,Van Dorpe J,Hoorens A

doi

10.1016/j.yexmp.2020.104442

subject

Has Abstract

pub_date

2020-08-01 00:00:00

pages

104442

eissn

0014-4800

issn

1096-0945

pii

S0014-4800(20)30100-3

journal_volume

115

pub_type

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