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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
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Research Article Oncology

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

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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

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Figure 2

Normal saline stimulates transient expansion of milky spots and neoangiogenesis in the omentum.

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Normal saline stimulates transient expansion of milky spots and neoangio...
Immune cells and microvessels were evaluated in omental tissues of untreated mice and mice at 1, 4, 7, and 14 days following i.p. administration of normal saline (n = 6 per group). Adult female C57BL/6 mice were used. (A) Representative images of CD45 staining (red) and CD31 staining (green) in omental tissues. Scale bar: 200 μm. (B) Abundance of immune cells, expressed as the percentage of area of CD45 staining within each tissue section. (C) Microvessel density, expressed as the number of CD31+ microvessels per 40× microscopic field. In B and C, an average score for each mouse was calculated by evaluating staining in 4–5 random and independent 40× microscopic fields. (D) Higher-magnification images of omental tissues showing prominent localization of microvessels in milky spots. Scale bar: 100 μm. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, by Dunnett’s multiple comparisons test compared with untreated mice (no lavage) in B and C.

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