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Our supporter Ruth Wilmott has designed a garden for the Chelsea Flower Show 2017, inspired by the research funded by Breast Cancer Now. But for one of our researchers, the inspiration goes both ways.
Ahead of the Chelsea Flower Show 2017, we caught up with Breast Cancer Now Scientific Fellow Dr Cristina Branco to hear about how her research has its roots in the biology of plants.
I am a biologist by training, specialising in how the normal machinery of our cells impact the way organs respond to disease – and in the case of cancer, may promote or prevent metastatic disease. I am also a college lecturer in Newnham College, University of Cambridge, a lecturer in Physiology, and mum to twin boys.
As a PhD student at the University of California, in collaboration with my home institute, the New University of Lisbon in Portugal, I studied how plants sense and respond to decreased oxygen concentrations, known as hypoxia.
Hypoxia is very relevant to plants, as it is for all organisms that rely upon oxygen to help make the energy they need.
When oxygen is limited – such as when soils are very compact, or flooded, or other organisms near the roots are competing for oxygen – plants need to make quick decisions to avoid any problems, responding in ways such as elongating their stems, or growing new roots.
In the meantime, plants need to make emergency metabolic changes that would allow energy to be produced using less or no oxygen, and in my research I was interested in how the plants managed this energy crisis. I was assessing how plants make the decisions that change their metabolism to allow survival: which genes are switched on, which proteins are produced, which functions will continue and which will stop to save energy.
The study of hypoxia in plants has an immediate application for optimizing crop yields – by understanding what it takes to help important crops survive a flood and minimise immense losses, particularly in countries that rely heavily on agriculture, such as monsoon-prone areas in south Asia. With unpredictable weather patterns, this has become a matter of priority.
Hypoxia is an energetic challenge for any living cell, and during my research I became very familiar with all the literature describing the phenomenon in animal cells. Scientists were already aware that hypoxia has a key role to play in the development of solid tumours such as breast cancer, and can increase the aggressiveness of the cancer.
I found this very intriguing: tumour cells are able to exploit this survival tool (hypoxia response pathway) to promote their own growth. The field was buzzing and I wanted to be part of it – it was that simple.
The technical demands were more or less straightforward, but it was a different world of model systems and experimental design approaches. Even though I felt familiar with the topic, I was by no means an expert – so there was a good six months or so when I was learning all I could about the field.
My plant colleagues and my supervisor thought it was a great idea, and that coming into the field with a naïve and unbiased view of cancer and hypoxia would probably deliver, with time, unique contributions and perspectives. I think at first, my new colleagues in the cancer field were apprehensive as to what I could offer – but the plant biology field was actually much more foreign to them than cancer biology was to me, so over time we all learnt to adapt.
Tumour cells multiply very quickly and so they exhaust the oxygen supply in the surrounding environment as the blood vessels cannot develop at a pace that matches the demand. Researchers over the years have found that, in breast cancer and other solid tumour types, the mechanism which is activated in response to hypoxia gives tumour cells an advantage: the more it is activated, the more aggressive and invasive the tumour is. We now know that this machinery is also activated at metastatic sites, to allow colonising cells to survive and multiply.
In cancer, I have learnt that although all cells are able to respond to hypoxia, exactly how cells respond is very context specific, and can vary between different types of cell. For example, in cancer cells, hypoxia promotes growth, but in other cells in the body it can result in activities that help the cancer, and other times in activities that resist the cancer.
In the context of breast cancer, I’ve been studying endothelial cells, which form the smallest blood vessels called capillaries – these are important because it’s through the blood that cancer cells can travel anywhere in the whole body. I’ve discovered that in endothelial cells, hypoxia can either promote the spread of breast cancer, or prevent it, depending on which pathway has been preferentially activated.
My work is now to understand how the response to hypoxia can be manipulated to stop the spread of breast cancer to different organs.
My specific goal is to study in detail the blood vessels at metastatic sites, for example in the lung, and identify how and why they cooperate with invading tumour cells. I have already seen that manipulating the hypoxia machinery in the capillaries in the lung can on its own inhibit the cancer cells’ ability to invade and multiply in the lungs. I hope my work will pave the way for developing therapies which stop the spread of breast cancer by empowering the normal cells to resist it.
Read more about Dr Cristina Branco's research
Find out more about the Breast Cancer Now Garden at the Chelsea Flower Show and book your tickets on the RHS website