When I started my PhD at the University of Edinburgh in Professor Val Brunton’s group in 2019 I was only just beginning to understand that breast cancer was more than one disease. It wasn’t until I actually applied for my PhD that I’d ever even heard of Lobular Breast Cancer despite it being the second most common subtype of breast cancer and sixth most common cancer in women overall, with over 8,000 women diagnosed each year in the UK.
Working with patient advocates from Lobular Breast Cancer UK (LBCUK) had a huge impact on me throughout my PhD. I’ve thoroughly enjoyed the two Research Partnership Days we’ve had at the University of Edinburgh with LBCUK, in particular showing patients around the lab. Whilst my research and knowledge is focused on working with cells, patients have a broad understanding about Lobular from basic science through to their own personal experiences in the clinic, offering an invaluable perspective on research.
Many of the best discussions I’ve had at conferences have been sparked by introductions from patient advocates. Working on lay summaries for patient advocates and presenting to patients has massively improved my science communication skills and made me think differently about my research.
Lobular tumour cells are distinctive because they grow in a single-file line instead 
of forming a lump like other subtypes of breast cancer. Because of the single-file growth pattern, Lobular cells come into contact with lots of ‘normal’ cells in the breast tissue. My research focuses on how one type of these ‘normal’ cells, called cancer-associated fibroblasts, communicate with the Lobular tumour cells and how this communication influences Lobular tumour cell growth and development.
My research found that a protein called IL-6 is secreted by cancer-associated fibroblasts and recognised by the Lobular tumour cells. IL-6 activates a protein called STAT3 in the tumour cells which then switches on lots of genes and causes cells to elongate and move faster in a dish, features that are associated with increased tumour spread in patients.
Looking at big clinical datasets, I found that Lobular tumours have much higher levels of IL-6 and STAT3 compared to ductal tumours, the more common subtype of breast cancer, suggesting that targeting IL-6 and STAT3 may particularly benefit Lobular patients.
We then wanted to test how IL-6 affects Lobular cells in a more complex model than just in cell lines. Estrogen receptor positive breast cancer is notoriously difficult to grow in mice, though recent work by Prof Cathrin Brisken’s research group has optimised a method for injecting human Lobular cell lines into mice that closely mimics the progression of the human disease.
However, mouse experiments can be expensive, are limited in the numbers of animals you can use and take up to a year to complete. In my PhD, I used zebrafish embryos and injected human Lobular tumour cells into them to assess how the cells spread and grow as an alternative and novel model for studying Lobular tumour cell behaviour.
This zebrafish embryo experiment only takes 2-4 days compared to up to a year for mouse experiments. The embryos are also transparent, so we can see the fluorescently labelled tumour cells moving throughout the embryos whilst the embryos are alive, allowing us to see every stage of metastasis. We also used zebrafish with green fluorescently-labelled blood vessels which allows us to see how the human tumour cells drive the formation of new zebrafish blood vessels. These zebrafish experiments bridge the gap between work on cells in the lab and mouse models, adding another experimental tool to our arsenal, helping us to further understand and identify specific treatments for this under-researched subtype of breast cancer.
I’ve seen an incredible increase in the amount of Lobular focused research, our knowledge of the disease, collaborations and awareness of Lobular Breast Cancer just in the four years of my PhD. This is in no small part due to the amazing work of patient advocates from all across the world who have raised awareness of Lobular Breast Cancer amongst the public, doctors and researchers, as well as facilitating essential research and patient care discussions. Working with patient advocates has made me a better scientist and I hope our work will contribute to the growing research into Lobular Breast Cancer and ultimately lead to improved treatments for this under-researched and unique disease.
ZEBRA FISH IMAGE NOTES
Zebrafish embryo model of metastasis. Human Lobular tumour cells (in red) are injected into the yolk sac of a two day old zebrafish embryo with fluorescently labelled blood vessels (in green). In this image, which was taken when the embryo was 4 days old (2 days after cells were injected), we can see that the lobular cells have spread away from the injection site (the large red tumour towards the bottom of the image) around the embryo. We can also see that an abnormal blood vessel has grown towards the tumour from the normal fish blood vessel systems.