Abstract
Introduction
Breast cancer (BC) is the most common cancer in UK with over 55000 women diagnosed each year. Advanced BC is associated with distant metastasis. The microenvironment plays a crucial role in the development of secondary disease influencing all the steps of the metastatic process, from the detachment from the primary tumour to the proliferation at the secondary organ. Solid tumours develop from a low number of cells in environments where oxygen (O2) is lower than atmospheric levels; therefore using BC models that mimic the physiological environments is crucial to understand tumour and somatic cell behaviours during BC dissemination.
Material and Methods
4T1 cells were grown in different O2 concentrations (21%, 10% and 5%); changes in viability, proliferation and migration ability were assessed at several time points. To mimic a physiological translatable model of BC metastasis, we injected low number of 4T1 cells grown at 5% O2 in the mammary fat pad of 8-week old BALB/c mice and distant metastatic sites (lungs and brain), were collected 2 and 6 weeks post injection.
Results and Discussions
Different concentrations of O2 alter the behaviour of BC cells in vitro. Viability and proliferation of 4T1 cells grown at physiological O2 (5%) are significantly reduced compared to cells grown in ambient air (p ≤ 0.0001). However, cell migration significantly increased (p≤ 0.0001) in BC cells grown at 5% O2. The in vivo model of BC used in our laboratory highlighted that primary tumours can be established injecting a low number of cancer cells in the mammary fat pad; importantly, the primary tumour burden 6 weeks post injection was comparable to that originated by injection of standard high cell numbers (p=0.72 andp=0.87) seen in the current literature. colony-initiating BC cells were isolated from distant organs as soon as 2 weeks after tumour cell implantation, modeling the very early stages of tumour progression concomitantly with early dissemination.
Conclusion
Physiological O2 levels influence the behaviour of BC cells in vitro and the initiation of the metastatic cascade in vivo can be achieved after the inoculation of a very low number of cancer cells. Further work will investigate the interaction of the metastasis-initiating tumour cells and the endothelial cells in physiological O2 to investigate how the use of physiologically relevant models could give a better understanding of the early stages of the metastatic cascade and the establishment of the pre-metastatic niche.
Breast cancer (BC) is the most common cancer in UK with over 55000 women diagnosed each year. Advanced BC is associated with distant metastasis. The microenvironment plays a crucial role in the development of secondary disease influencing all the steps of the metastatic process, from the detachment from the primary tumour to the proliferation at the secondary organ. Solid tumours develop from a low number of cells in environments where oxygen (O2) is lower than atmospheric levels; therefore using BC models that mimic the physiological environments is crucial to understand tumour and somatic cell behaviours during BC dissemination.
Material and Methods
4T1 cells were grown in different O2 concentrations (21%, 10% and 5%); changes in viability, proliferation and migration ability were assessed at several time points. To mimic a physiological translatable model of BC metastasis, we injected low number of 4T1 cells grown at 5% O2 in the mammary fat pad of 8-week old BALB/c mice and distant metastatic sites (lungs and brain), were collected 2 and 6 weeks post injection.
Results and Discussions
Different concentrations of O2 alter the behaviour of BC cells in vitro. Viability and proliferation of 4T1 cells grown at physiological O2 (5%) are significantly reduced compared to cells grown in ambient air (p ≤ 0.0001). However, cell migration significantly increased (p≤ 0.0001) in BC cells grown at 5% O2. The in vivo model of BC used in our laboratory highlighted that primary tumours can be established injecting a low number of cancer cells in the mammary fat pad; importantly, the primary tumour burden 6 weeks post injection was comparable to that originated by injection of standard high cell numbers (p=0.72 andp=0.87) seen in the current literature. colony-initiating BC cells were isolated from distant organs as soon as 2 weeks after tumour cell implantation, modeling the very early stages of tumour progression concomitantly with early dissemination.
Conclusion
Physiological O2 levels influence the behaviour of BC cells in vitro and the initiation of the metastatic cascade in vivo can be achieved after the inoculation of a very low number of cancer cells. Further work will investigate the interaction of the metastasis-initiating tumour cells and the endothelial cells in physiological O2 to investigate how the use of physiologically relevant models could give a better understanding of the early stages of the metastatic cascade and the establishment of the pre-metastatic niche.
| Original language | English |
|---|---|
| Publication status | Published - 02 Mar 2020 |
| Event | EACR-AACR Basic and Translational Research Conference - Tumor Microenvironment: Tumor Microenvironment - Centro de Congressos de Lisboa, Lisbon, Portugal Duration: 02 Mar 2020 → 04 Mar 2020 https://www.eaa2020.org |
Conference
| Conference | EACR-AACR Basic and Translational Research Conference - Tumor Microenvironment |
|---|---|
| Country/Territory | Portugal |
| City | Lisbon |
| Period | 02/03/2020 → 04/03/2020 |
| Internet address |
