Hannah Smith, Dr Janos Kanzler, Professor Steve Beers, Professor Juliet Gray 

University of Southampton

Part funded PhD project (2019-2022)

BACKGROUND TO THE RESEARCH PROJECT

The most common bone cancer in young people is osteosarcoma. It is an aggressive cancer and unfortunately treatment hasn't progressed much in 40 years. This team at Southampton have created a laboratory model of osteosarcoma to try and better understand how this disease arises from normal bone cells and to test potential new therapies to prevent the growth of this cancer. 

The origin of osteosarcoma cells in bone is still unknown, and this lack of understanding prevents early detection of this disease. Bone grows from specialised cells located in the bone marrow (the soft, jelly-like tissue found in the centre of most bones). In Hannah’s PhD project, the team were interested to see if there were differences between the cells of the bone marrow from distinct locations of the long thigh bone and whether these differences might impact their ability to initiate disease. 

To do this, they collected and grew these specialised bone marrow cells from different regions of human bones (these were called red and yellow bone marrow) where osteosarcoma cancers tend to develop. They then looked at the ability of these cells to change into three types of cells, osteoblasts which make bone, adipocytes which make fat and chondrocytes which make cartilage, all of which are critical in shaping, growing, and repairing our skeleton particularly at a youthful age. The team compared the characteristics of these cells with two known osteosarcoma cells (called Saos-2 and MG63). From Hannah’s studies, she found that bone marrow specialised cells changed differently when stimulated depending on the region of the bone they came from. Improved understanding of the origin and the bone environment where these osteosarcoma cells develop could allow for earlier detection and treatment of the disease to improve the patients overall outcome.

KEY RESULTS

Why and how osteosarcoma cells start growing is still unknown, and this lack of understanding prevents early detection of this disease. Bone grows from specialised cells located in the bone marrow (The soft, jelly-like tissue found in the centre of most bones). 

During Hannah’s PhD, the team were interested to see if there were differences between the bone marrow cells from distinct locations of the femur which might impact their ability to initiate disease. They collected and grew these specialised bone marrow cells from two different regions (called red and yellow bone marrow) and found that there were big differences in how they changed into cells which make bone, fat, and cartilage. 

They also looked at two types of osteosarcoma cancer cells and how similar they were to the bone marrow cells, with one called Saos-2 showing a similar ability to form bone like the bone marrow cells.

After incubating the bone cylinders they were successfully able to look at whether there was bone growth or loss, as well as changes in their features/traits. They identified that the cells stayed alive and were interacting in this model to recreate the human tumour.

Finally, the drug mifamurtide was tested on the bone model, and it was found that it resulted in a lower bone volume and changes in the model’s characteristics, which will help in understanding why not all patients respond to mifamurtide.

OUTPUTS

Publications:

*Smith, H. L., Beers, S. A., Kanczler, J. M., & Gray, J. C. Developing a 3D model of osteosarcoma to investigate cancer mechanisms and evaluate treatments. Submitted for publication Dec 2023 and under revision.

*Smith, H. L., Gray, J. C., Beers, S. A., & Kanczler, J. M. (2023). Tri-Lineage Differentiation Potential of Osteosarcoma Cell Lines and Human Bone Marrow Stromal Cells from Different Anatomical Locations. Int J Mol Sci, 24(4). https://doi.org/10.3390/ijms24043667

*Smith, H. L., Beers, S. A., Gray, J. C., & Kanczler, J. M. (2020). The Role of Pre-Clinical 3-Dimensional Models of Osteosarcoma. Int J Mol Sci, 21(15). https://doi.org/10.3390/ijms21155499 

*Smith, H. L., Kanczler, J. M., Gray, J. C., & Beers, S. A. Monocyte Derived Macrophages: Peripheral Blood vs Bone Marrow. In final preparation for submission. Estimated End of Feb 2024.

Presentations:

2023 - Hannah’s Willberry Wonder Pony Charity Symposium - Oral presentation

2022 - Centre for Human Development, Stem Cells and Regeneration conference Oral presentation

2020 - Bone Research Society: Osteosarcoma cells modulate skeletal stromal cell phenotype- site specific interactions. - Poster presentation

2020 - Cancer Research Club -Oral Presentation

2019 - 11th Annual Cancer Sciences Unit Conference - Poster Presentation