Normal saline remodels the omentum and stimulates its receptivity for transcoelomic metastasis
Hironari Akasaka, WonJae Lee, Song Yi Ko, Ernst Lengyel, Honami Naora
Hironari Akasaka, WonJae Lee, Song Yi Ko, Ernst Lengyel, Honami Naora
View: Text | PDF
Research Article Oncology

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

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 1

Normal saline is prominently absorbed by the omentum and exfoliates its mesothelium.

Options: View larger image (or click on image) Download as PowerPoint
Normal saline is prominently absorbed by the omentum and exfoliates its ...
(A and B) Absorption of normal saline by peritoneal fat tissues. (A) Representative images of omental, mesenteric, and gonadal fat tissues at 1 hour following i.p. administration of normal saline (12.5 mL/kg) containing Evans Blue dye to mice. Scale bar: 10 mm. (B) Quantification of dye in each tissue. Data of n = 5 mice are shown. (C) Representative images of H&E-stained sections of peritoneal fat tissues of untreated mice and mice at the indicated time points following i.p. administration of normal saline. Scale bar: 200 μm. Tissues of n = 6 mice per group were evaluated. (D and E) WT1+ cells in peritoneal fat tissues of untreated mice and mice at day 1 and day 7 following saline administration (n = 6 per group). (D) Representative images of immunofluorescence staining of WT1 (shown in green). Tissues were counterstained with DAPI. Scale bar: 200 μm. (E) Abundance of WT1+ cells, expressed as the percentage of area within each tissue. An average score for each tissue of each mouse was calculated by evaluating WT1 staining in 4–5 random and independent 40× microscopic fields. Adult female C57BL/6 mice were used in A–E. **P < 0.01, ****P < 0.0001, by Tukey’s multiple comparisons test in B and by Dunnett’s multiple comparisons test compared with untreated mice in E.