Myeloid-derived suppressor cells are implicated in regulating permissiveness for tumor metastasis during mouse gestation
Laetitia A. Mauti, … , Paolo Provero, Ivan Stamenkovic
Laetitia A. Mauti, … , Paolo Provero, Ivan Stamenkovic
Published July 1, 2011; First published June 6, 2011
Citation Information: J Clin Invest. 2011;121(7):2794-2807. https://doi.org/10.1172/JCI41936.
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Research Article Oncology

Myeloid-derived suppressor cells are implicated in regulating permissiveness for tumor metastasis during mouse gestation

Abstract

Metastasis depends on the ability of tumor cells to establish a relationship with the newly seeded tissue that is conducive to their survival and proliferation. However, the factors that render tissues permissive for metastatic tumor growth have yet to be fully elucidated. Breast tumors arising during pregnancy display early metastatic proclivity, raising the possibility that pregnancy may constitute a physiological condition of permissiveness for tumor dissemination. Here we have shown that during murine gestation, metastasis is enhanced regardless of tumor type, and that decreased NK cell activity is responsible for the observed increase in experimental metastasis. Gene expression changes in pregnant mouse lung and liver were shown to be similar to those detected in premetastatic sites and indicative of myeloid cell infiltration. Indeed, myeloid-derived suppressor cells (MDSCs) accumulated in pregnant mice and exerted an inhibitory effect on NK cell activity, providing a candidate mechanism for the enhanced metastatic tumor growth observed in gestant mice. Although the functions of MDSCs are not yet understood in the context of pregnancy, our observations suggest that they may represent a shared mechanism of immune suppression occurring during gestation and tumor growth.

Authors

Laetitia A. Mauti, Marie-Aude Le Bitoux, Karine Baumer, Jean-Christophe Stehle, Dela Golshayan, Paolo Provero, Ivan Stamenkovic

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Figure 2

Increased metastasis in pregnant mice is independent of tumor cell type and mouse strain and holds true for spontaneous metastasis formation.

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Increased metastasis in pregnant mice is independent of tumor cell type ...
(A–D) 7 × 105 luciferase-expressing HT1080 tumor cells were injected into the tail vein of day-16 pregnant and virgin NOD/SCID mice. (E–H) 7 × 105 luciferase-expressing TA3 tumor cells were injected into the tail vein of syngeneic day-16 pregnant and virgin A/Jax mice. (I–K) 5 × 105 luciferase-expressing LLC cells were injected s.c. into 21 virgin C57BL/6 mice, then breeding was started, yielding 13 pregnant animals. Primary tumors were resected 11 days after injection, and mice were followed up for lung metastasis development for 33 days. (A, E, and I) Evolution of the bioluminescent signal from the entire body surface of mice. *P < 0.05, **P < 0.01, ***P < 0.001, 2-way repeated-measures ANOVA with Bonferroni post-test. (B, F, and J) Representative images of formalin-fixed lungs. Scale bars: 5 mm. (C and G) Histomorphometry of lung sections (4 fields per mouse). **P < 0.01, ***P < 0.001, unpaired 2-tailed t test. (D and H) Representative lung histology. Scale bars: 1 mm. (K) Proportion of mice with macroscopic lung metastases. *P < 0.05, column statistics.