The bone metastasis niche in breast cancer-potential overlap with the haematopoietic stem cell niche in vivo
Background: Bone metastasis is one of the most common complications of advanced breast cancer. During dissemination to bone, breast cancer cells locate in a putative ‘metastatic niche’, a microenvironment that regulates the colonisation, maintenance of tumour cell dormancy and subsequent tumour grow...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-08-01
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| Series: | Journal of Bone Oncology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212137419300387 |
| _version_ | 1819238334024646656 |
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| author | Gloria Allocca Russell Hughes Ning Wang Hannah K Brown Penelope D Ottewell Nicola J Brown Ingunn Holen |
| author_facet | Gloria Allocca Russell Hughes Ning Wang Hannah K Brown Penelope D Ottewell Nicola J Brown Ingunn Holen |
| author_sort | Gloria Allocca |
| collection | DOAJ |
| description | Background: Bone metastasis is one of the most common complications of advanced breast cancer. During dissemination to bone, breast cancer cells locate in a putative ‘metastatic niche’, a microenvironment that regulates the colonisation, maintenance of tumour cell dormancy and subsequent tumour growth. The precise location and composition of the bone metastatic niche is not clearly defined. We have used in vivo models of early breast cancer dissemination to provide novel evidence that demonstrates overlap between endosteal, perivascular, HSC and the metastatic niche in bone.Methods: Estrogen Receptor (ER) +ve and -ve breast cancer cells were labelled with membrane dyes Vybrant-DiD and Vybrant-CM-DiI and injected via different routes in BALBc/nude mice of different ages. Two-photon microscopy was used to detect and quantitate tumour cells and map their location within the bone microenvironment as well as their distance to the nearest bone surface compared to the nearest other tumour cell. To investigate whether the metastatic niche overlapped with the HSC niche, animals were pre-treated with the CXCR4 antagonist AMD3100 to mobilise hematopoietic (HSCs) prior to injection of breast cancer cells.Results: Breast cancer cells displayed a characteristic pattern of homing in the long bones, with the majority of tumour cells seeded in the trabecular regions, regardless of the route of injection, cell-line characteristics (ER status) or animal age. Breast cancer cells located in close proximity to the nearest bone surface and the average distance between individual tumour cells was higher than their distance to bone. Mobilisation of HSCs from the niche to the circulation prior to injection of cell lines resulted in increased numbers of tumour cells disseminated in trabecular regions.Conclusion: Our data provide evidence that homing of breast cancer cells is independent of their ER status and that the breast cancer bone metastasis niche is located within the trabecular region of bone, an area rich in osteoblasts and microvessels. The increased number of breast cancer cells homing to bone after mobilisation of HSCs suggests that the HSC and the bone metastasis niche overlap. Keywords: Bone metastasis, Animal models, Breast cancer, Hematopoietic stem cell |
| first_indexed | 2024-12-23T13:34:34Z |
| format | Article |
| id | doaj.art-12c2aea1c17749b38ad1953739c04483 |
| institution | Directory Open Access Journal |
| issn | 2212-1374 |
| language | English |
| last_indexed | 2024-12-23T13:34:34Z |
| publishDate | 2019-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Bone Oncology |
| spelling | doaj.art-12c2aea1c17749b38ad1953739c044832022-12-21T17:45:03ZengElsevierJournal of Bone Oncology2212-13742019-08-0117The bone metastasis niche in breast cancer-potential overlap with the haematopoietic stem cell niche in vivoGloria Allocca0Russell Hughes1Ning Wang2Hannah K Brown3Penelope D Ottewell4Nicola J Brown5Ingunn Holen6Department of Oncology and Metabolism, Medical School, University of Sheffield, UKDepartment of Oncology and Metabolism, Medical School, University of Sheffield, UKDepartment of Oncology and Metabolism, Medical School, University of Sheffield, UKDepartment of Oncology and Metabolism, Medical School, University of Sheffield, UKDepartment of Oncology and Metabolism, Medical School, University of Sheffield, UKDepartment of Oncology and Metabolism, Medical School, University of Sheffield, UKCorresponding author.; Department of Oncology and Metabolism, Medical School, University of Sheffield, UKBackground: Bone metastasis is one of the most common complications of advanced breast cancer. During dissemination to bone, breast cancer cells locate in a putative ‘metastatic niche’, a microenvironment that regulates the colonisation, maintenance of tumour cell dormancy and subsequent tumour growth. The precise location and composition of the bone metastatic niche is not clearly defined. We have used in vivo models of early breast cancer dissemination to provide novel evidence that demonstrates overlap between endosteal, perivascular, HSC and the metastatic niche in bone.Methods: Estrogen Receptor (ER) +ve and -ve breast cancer cells were labelled with membrane dyes Vybrant-DiD and Vybrant-CM-DiI and injected via different routes in BALBc/nude mice of different ages. Two-photon microscopy was used to detect and quantitate tumour cells and map their location within the bone microenvironment as well as their distance to the nearest bone surface compared to the nearest other tumour cell. To investigate whether the metastatic niche overlapped with the HSC niche, animals were pre-treated with the CXCR4 antagonist AMD3100 to mobilise hematopoietic (HSCs) prior to injection of breast cancer cells.Results: Breast cancer cells displayed a characteristic pattern of homing in the long bones, with the majority of tumour cells seeded in the trabecular regions, regardless of the route of injection, cell-line characteristics (ER status) or animal age. Breast cancer cells located in close proximity to the nearest bone surface and the average distance between individual tumour cells was higher than their distance to bone. Mobilisation of HSCs from the niche to the circulation prior to injection of cell lines resulted in increased numbers of tumour cells disseminated in trabecular regions.Conclusion: Our data provide evidence that homing of breast cancer cells is independent of their ER status and that the breast cancer bone metastasis niche is located within the trabecular region of bone, an area rich in osteoblasts and microvessels. The increased number of breast cancer cells homing to bone after mobilisation of HSCs suggests that the HSC and the bone metastasis niche overlap. Keywords: Bone metastasis, Animal models, Breast cancer, Hematopoietic stem cellhttp://www.sciencedirect.com/science/article/pii/S2212137419300387 |
| spellingShingle | Gloria Allocca Russell Hughes Ning Wang Hannah K Brown Penelope D Ottewell Nicola J Brown Ingunn Holen The bone metastasis niche in breast cancer-potential overlap with the haematopoietic stem cell niche in vivo Journal of Bone Oncology |
| title | The bone metastasis niche in breast cancer-potential overlap with the haematopoietic stem cell niche in vivo |
| title_full | The bone metastasis niche in breast cancer-potential overlap with the haematopoietic stem cell niche in vivo |
| title_fullStr | The bone metastasis niche in breast cancer-potential overlap with the haematopoietic stem cell niche in vivo |
| title_full_unstemmed | The bone metastasis niche in breast cancer-potential overlap with the haematopoietic stem cell niche in vivo |
| title_short | The bone metastasis niche in breast cancer-potential overlap with the haematopoietic stem cell niche in vivo |
| title_sort | bone metastasis niche in breast cancer potential overlap with the haematopoietic stem cell niche in vivo |
| url | http://www.sciencedirect.com/science/article/pii/S2212137419300387 |
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