Immune Milieu Established by Postpartum Liver Involution Promotes Breast Cancer Liver Metastasis
In rodents, we identified a physiologic process within the normal liver that creates a pre-metastatic niche. This physiology is weaning-induced liver involution, characterized by hepatocyte cell death, immune influx, and extracellular matrix remodeling. Here, using weaning-induced liver involution a...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-04-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/7/1698 |
| _version_ | 1797538889587490816 |
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| author | Alexandra Q. Bartlett Nathan D. Pennock Alex Klug Pepper Schedin |
| author_facet | Alexandra Q. Bartlett Nathan D. Pennock Alex Klug Pepper Schedin |
| author_sort | Alexandra Q. Bartlett |
| collection | DOAJ |
| description | In rodents, we identified a physiologic process within the normal liver that creates a pre-metastatic niche. This physiology is weaning-induced liver involution, characterized by hepatocyte cell death, immune influx, and extracellular matrix remodeling. Here, using weaning-induced liver involution as a model of a physiologically regulated pro-metastatic niche, we investigate how liver involution supports breast cancer metastasis. Liver metastases were induced in BALB/c immune competent hosts by portal vein injection of D2OR (low metastatic) or D2A1 (high metastatic) mouse mammary tumor cells. Tumor incidence and multiplicity increased in involution hosts with no evidence of a proliferation advantage. D2OR tumor cell extravasation, seeding, and early survival were not enhanced in the involuting group compared to the nulliparous group. Rather, the involution metastatic advantage was observed at 14 days post tumor cell injection. This metastatic advantage associated with induction of immune tolerance in the involution host liver, reproductive state dependent intra-tumoral immune composition, and CD8-dependent suppression of metastases in nulliparous hosts. Our findings suggest that the normal postpartum liver is in an immune suppressed state, which can provide a pro-metastatic advantage to circulating breast cancer cells. Potential relevance to women is suggested as a postpartum diagnosis of breast cancer is an independent predictor of liver metastasis. |
| first_indexed | 2024-03-10T12:37:36Z |
| format | Article |
| id | doaj.art-4966d5576e5d46a9a02e202c40422e6b |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T12:37:36Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-4966d5576e5d46a9a02e202c40422e6b2023-11-21T14:06:55ZengMDPI AGCancers2072-66942021-04-01137169810.3390/cancers13071698Immune Milieu Established by Postpartum Liver Involution Promotes Breast Cancer Liver MetastasisAlexandra Q. Bartlett0Nathan D. Pennock1Alex Klug2Pepper Schedin3Department of Cell, Developmental, and Cancer Biology, Oregon Health & Science University, Portland, OR 97239, USADepartment of Cell, Developmental, and Cancer Biology, Oregon Health & Science University, Portland, OR 97239, USADepartment of Cell, Developmental, and Cancer Biology, Oregon Health & Science University, Portland, OR 97239, USADepartment of Cell, Developmental, and Cancer Biology, Oregon Health & Science University, Portland, OR 97239, USAIn rodents, we identified a physiologic process within the normal liver that creates a pre-metastatic niche. This physiology is weaning-induced liver involution, characterized by hepatocyte cell death, immune influx, and extracellular matrix remodeling. Here, using weaning-induced liver involution as a model of a physiologically regulated pro-metastatic niche, we investigate how liver involution supports breast cancer metastasis. Liver metastases were induced in BALB/c immune competent hosts by portal vein injection of D2OR (low metastatic) or D2A1 (high metastatic) mouse mammary tumor cells. Tumor incidence and multiplicity increased in involution hosts with no evidence of a proliferation advantage. D2OR tumor cell extravasation, seeding, and early survival were not enhanced in the involuting group compared to the nulliparous group. Rather, the involution metastatic advantage was observed at 14 days post tumor cell injection. This metastatic advantage associated with induction of immune tolerance in the involution host liver, reproductive state dependent intra-tumoral immune composition, and CD8-dependent suppression of metastases in nulliparous hosts. Our findings suggest that the normal postpartum liver is in an immune suppressed state, which can provide a pro-metastatic advantage to circulating breast cancer cells. Potential relevance to women is suggested as a postpartum diagnosis of breast cancer is an independent predictor of liver metastasis.https://www.mdpi.com/2072-6694/13/7/1698metastatic nicheliver metastasisbreast cancerliver involution |
| spellingShingle | Alexandra Q. Bartlett Nathan D. Pennock Alex Klug Pepper Schedin Immune Milieu Established by Postpartum Liver Involution Promotes Breast Cancer Liver Metastasis Cancers metastatic niche liver metastasis breast cancer liver involution |
| title | Immune Milieu Established by Postpartum Liver Involution Promotes Breast Cancer Liver Metastasis |
| title_full | Immune Milieu Established by Postpartum Liver Involution Promotes Breast Cancer Liver Metastasis |
| title_fullStr | Immune Milieu Established by Postpartum Liver Involution Promotes Breast Cancer Liver Metastasis |
| title_full_unstemmed | Immune Milieu Established by Postpartum Liver Involution Promotes Breast Cancer Liver Metastasis |
| title_short | Immune Milieu Established by Postpartum Liver Involution Promotes Breast Cancer Liver Metastasis |
| title_sort | immune milieu established by postpartum liver involution promotes breast cancer liver metastasis |
| topic | metastatic niche liver metastasis breast cancer liver involution |
| url | https://www.mdpi.com/2072-6694/13/7/1698 |
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