Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Physician-Scientist Development
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • In-Press Preview
    • Resource and Technical Advances
    • Clinical Research and Public Health
    • Research Letters
    • Editorials
    • Perspectives
    • Physician-Scientist Development
    • Reviews
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Resource and Technical Advances
  • Clinical Research and Public Health
  • Research Letters
  • Editorials
  • Perspectives
  • Physician-Scientist Development
  • Reviews
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Transfers
  • Advertising
  • Job board
  • Contact
Normal saline remodels the omentum and stimulates its receptivity for transcoelomic metastasis
Hironari Akasaka, … , Ernst Lengyel, Honami Naora
Hironari Akasaka, … , Ernst Lengyel, Honami Naora
Published June 22, 2023
Citation Information: JCI Insight. 2023;8(12):e167336. https://doi.org/10.1172/jci.insight.167336.
View: Text | PDF
Research Article Oncology

Normal saline remodels the omentum and stimulates its receptivity for transcoelomic metastasis

  • Text
  • PDF
Abstract

The omentum contains immune cell structures called milky spots that are niches for transcoelomic metastasis. It is difficult to remove the omentum completely, and there are no effective strategies to minimize the risk of colonization of preserved omental tissues by cancer cells that circulate in the peritoneal fluid. Normal saline is commonly administered into the peritoneal cavity for diagnostic and intraoperative lavage. Here we show that normal saline, when administered into the peritoneal cavity of mice, is prominently absorbed by the omentum, exfoliates its mesothelium, and induces expression of CX3CL1, the ligand for CX3CR1, within and surrounding the omental vasculature. Studies using CX3CR1-competent and CX3CR1-deficient mice showed that the predominant response in the omentum following saline administration is an accumulation of CX3CR1+ monocytes/macrophages that expand milky spots and promote neoangiogenesis within these niches. Moreover, saline administration promoted the implantation of cancer cells of ovarian and colorectal origin onto the omentum. By contrast, these deleterious effects were not observed following i.p. administration of lactated Ringer’s solution. Our findings suggest that normal saline stimulates the receptivity of the omentum for cancer cells and that the risk of colonization can be minimized by using a biocompatible crystalloid for lavage procedures.

Authors

Hironari Akasaka, WonJae Lee, Song Yi Ko, Ernst Lengyel, Honami Naora

×

Figure 5

Normal saline increases expression of CX3CL1 within and surrounding the omental vasculature.

Options: View larger image (or click on image) Download as PowerPoint
Normal saline increases expression of CX3CL1 within and surrounding the ...
(A–E) CX3CL1 expression in omental tissues of untreated mice and at day 1 following saline administration. Adult female C57BL/6 mice were used. (A) Total CX3CL1 content in omental tissues, determined by ELISA. Data of n = 5 mice per group are shown. (B and C) Representative images of immunofluorescence staining of CD45 and CX3CL1 (B), and CD31 and CX3CL1 (C). Scale bar: 100 μm. (D) Representative histogram plots of staining of membrane-bound CX3CL1 within gated CD45+, CD31+, and CD45–CD31– populations. (E) Percentages of CX3CL1+ cells within the indicated gated populations. Data of n = 6 mice per group are shown. (F) GFP+ blood monocytes of Cx3cr1+/GFP mice were assayed for chemotaxis toward equivalent numbers of CD45– cells of the stromal vascular fraction that were sorted from omenta of C57BL/6 mice left untreated and at day 1 following saline administration. Shown are data of 3 independent assays, where each assay used omental stromal vascular cells from a different mouse. (G) Representative images of omental tissues of adult female Cx3cr1+/GFP mice that were left untreated and at day 7 following saline administration. Scale bar: 200 μm. Tissues of n = 5 mice per group were evaluated. *P < 0.05, **P < 0.01, by unpaired 2-tailed Student’s t test in A, E and F.

Copyright © 2025 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts