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. 2013 Nov;6(11):1182-93.
doi: 10.1158/1940-6207.CAPR-13-0227. Epub 2013 Sep 10.

The parity-associated microenvironmental niche in the omental fat band is refractory to ovarian cancer metastasis

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The parity-associated microenvironmental niche in the omental fat band is refractory to ovarian cancer metastasis

Courtney A Cohen et al. Cancer Prev Res (Phila). 2013 Nov.

"V体育2025版" Abstract

Ovarian cancer is an insidious and aggressive disease of older women, typically undiscovered before peritoneal metastasis due to its asymptomatic nature and lack of early detection tools. Epidemiologic studies suggest that child-bearing (parity) is associated with decreased ovarian cancer risk, although the molecular mechanisms responsible for this phenomenon have not been delineated. Ovarian cancer preferentially metastasizes to the omental fat band (OFB), a secondary lymphoid organ that aids in filtration of the peritoneal serous fluid (PSF) and helps combat peritoneal infections. In the present study, we assessed how parity and age impact the immune compositional profile in the OFB of mice, both in the homeostatic state and as a consequence of peritoneal implantation of ovarian cancer. Using fluorescence-activated cell sorting analysis and quantitative real-time PCR, we found that parity was associated with a significant reduction in omental monocytic subsets and B1-B lymphocytes, correlating with reduced homeostatic expression levels of key chemoattractants and polarization factors (Ccl1, Ccl2, Arg1, and Cxcl13). Of note, parous animals exhibited significantly reduced tumor burden following intraperitoneal implantation compared with nulliparous animals. This was associated with a reduction in tumor-associated neutrophils and macrophages, as well as in the expression levels of their chemoattractants (Cxcl1 and Cxcl5) in the OFB and PSF. These findings define a preexisting "parity-associated microenvironmental niche" in the OFB that is refractory to metastatic tumor seeding and outgrowth. Future studies designed to manipulate this niche may provide a novel means to mitigate peritoneal dissemination of ovarian cancer. VSports手机版.

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Disclosure:

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Parity-associated differences in the cellularity of the OFBs of young adult nulliparous (yNP), mature adult nulliparous (aNP) and adult parous mice (aP) mice. A) Whole tissue OFB weight. B) Number of cells in the SVF isolated from digested OFB. C) CD45+ population in OFB SVF. D) Gene expression profile of OFB. *p<0.05. **p<0.01.
Figure 2
Figure 2
The OFB displays parity-associated differences in leukocyte populations. A) CD45+ leukocytes in the SVF of OFBs harvested from young adult nulliparous (yNP), mature adult nulliparous (aNP) and mature parous mice (aP) were separated into regions R1 (lymphocytes) and R2 (monocytes/granulocytes) for further analysis. B) Distribution of R1:R2 populations in OFBs. C) Overall immune cell populations in OFBs. D) CD3+ subsets within OFBs. E) CD19+ subsets within OFBs. F) Monocyte/granulocyte subsets within OFBs. *p<0.05, **p<0.01
Figure 3
Figure 3
Parity mitigates tumor burden and metastasis-associated influx of stromal cells to the OFB following MOSEFFL intraperitoneal implantation. Direct comparison of the SVF of OFBs obtained from young adult nulliparous (yNP) and mature adult parous (aP) mice without (PBS) or following MOSE-LFFLv implantation. A) Peritoneal Cancer Index (PCI) (n =10). B) FFL gene expression in OFB of tumor-bearing mice compared to their PBS-injected counterparts. C) Whole tissue OFB weight. D) Total yield of SVF cells isolated from digested OFBs. E) Percentage of CD45+ population in the OFB SVF. *p<0.05. **p<0.01.
Figure 4
Figure 4
Ovarian cancer outgrowth elicits macrophage and neutrophil influx into the OFB of young adult nulliparous (yNP) mice. A) Comparative distribution of R1(lymphocytes):R2(monocyte/granulocyte) CD45+ populations in yNP and mature adult parous (aP) OFB as a consequence of cancer dissemination. B–D) Immune cell changes in the OFB of yNP mice following MOSE-LFFLv seeding and outgrowth were determined by FACS analysis. Overall leukocyte profile (B) and changes within CD3+ subsets (C) CD19+ subsets (D) and monocyte/granulocyte subsets (E) are depicted. F) Gene expression changes in the OFBs of MOSE-LFFLv-bearing yNP mice compared to age-matched naïve mice (yNP PBS). All genes displayed were significantly (p<0.05) changed from PBS control. Statistical significance (p-values) are provided or denoted by * p<0.05. **p<0.01.
Figure 5
Figure 5
Parity mitigates ovarian cancer outgrowth-associated influx of macrophages and neutrophils to the OFB. Immune cell changes in the OFB of mature adult (aP) mice following MOSE-LFFLv seeding and outgrowth were determined by FACS analysis. Overall leukocyte population changes in the OFB (A) as well as cancer-associated changes within CD3+ subsets (B), CD19+ subsets (C) and monocyte/granulocyte subsets (D) are presented. F) Gene expression changes in the OFBs of MOSE-LFFLv-bearing aP mice compared to age-matched naïve mice (aP PBS). All genes displayed were significantly changed from PBS controls, *p<0.05. **p<0.01.
Figure 6
Figure 6
Gene expression signatures in the OFB associated with age, parity, or cancer cell seeding and outgrowth. Venn diagram representing significantly altered genes (*), p<0.05, and genes trending towards significance p=0.05–0.08. White boxes indicate increased expression, grey boxes indicates decreased expression.

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