RRC ID 75753
Author Sihombing AM, Murata S, Shimoji M, Miyake T, Takebayashi K, Kodama H, Tokuda A, Kojima M, Ueki T, Kitamura N, Kitamura M, Mekata E, Tani M.
Title CD44-positive Cancer Stem-like Cells as a Potential Source of Peritoneal Metastasis After Surgery.
Journal Anticancer Res
Abstract BACKGROUND/AIM:The role of CD44 in gastric cancer-derived peritoneal metastasis is currently unknown. It was previously shown that viable, tumorigenic cancer cells are spilled into the peritoneal cavity during surgery, providing a potential cause of peritoneal recurrence after surgery. The purpose of this study was to elucidate the mechanism of peritoneal metastasis of gastric cancer through the expression of CD44 and to propose a method for preventing peritoneal recurrence.
MATERIALS AND METHODS:Gastric cancer cell line MKN-45 was sorted into CD44+ and CD44- cells and then injected intraperitoneally into NOD/ShiJic-scidJcl mice. Differences in tumor-initiating capacity between the two groups were assessed using in vivo limiting dilution assays. Tumors harvested from both groups were examined for CD44 and ALDH1A1 expression using immunohistochemistry. The effects of CD44 blockade with anti-CD44 antibody on cell invasion and peritoneal metastasis formation in vivo were assessed.
RESULTS:CD44+ cells showed significantly higher efficiency in initiating peritoneal tumor than CD44- cells. Blockade of CD44 significantly reduced peritoneal dissemination of CD44+ cells in vivo, indicating that the CD44 function of intraperitoneally disseminated cancer cells helped promote the formation of peritoneal metastasis. The margin of established tumors showed clusters of cells co-expressing CD44 and ALDH1A1. Peritoneally administered CD44- cells resulted in peritoneal metastases consisting of CD44+ and CD44- cancer cells.
CONCLUSION:CD44 expressing cells are a potential source of peritoneal metastasis after surgery and could be a promising target for preventing peritoneal recurrence.
Volume 43(6)
Pages 2491-2500
Published 2023-6-1
DOI 10.21873/anticanres.16416
PII 43/6/2491
PMID 37247920
MeSH Animals Cell Line, Tumor Hyaluronan Receptors / metabolism Mice Mice, Inbred NOD Neoplastic Stem Cells / metabolism Peritoneal Neoplasms* / pathology Peritoneum / pathology Stomach Neoplasms* / pathology
IF 1.994
Human and Animal Cells MKN45(RCB1001)