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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 3

Normal saline increases numbers of omental CD11bintF4/80lo SPM-like cells that predominantly express CX3CR1.

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Normal saline increases numbers of omental CD11bintF4/80lo SPM-like cell...
Flow cytometric analysis of immune cell populations in omental tissues of untreated mice and mice at day 1 and day 7 following i.p. administration of normal saline (n = 6 per group). Adult female C57BL/6 mice were used. (A) Representative contour plots of forward scatter and CD11b staining within gated CD45+ cells, showing abundance of CD11blo and CD11bhi/int populations. (B) Numbers of CD11blo and CD11bhi/int cells per omental fat band. (C) Representative plots of CD11b and F4/80 staining within gated CD45+ cells, showing abundance of CD11bhiF4/80hi and CD11bintF4/80lo populations. (D) Numbers of CD11bhiF4/80hi and CD11bint F4/80lo cells per omental fat band. (E) Representative contour plots of ICAM2 and MHCII staining within gated CD11bhiF4/80hi and CD11bintF4/80lo populations. The abundance of MHCII+ and MHCII– cells within each population is indicated. (F) Numbers of CD11bintF4/80lo MHCII+ and CD11bintF4/80loMHCII– cells per omental fat band. (G) Percentages of Ly6Chi, CCR2+, and CX3CR1+ cells within gated CD11bintF4/80loMHCII+ and CD11bintF4/80loMHCII– subpopulations. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, by Dunnett’s multiple comparisons test compared with untreated mice for each given cell population in B and D and by Tukey’s multiple comparisons test in F and G.

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