DKK 12 million grant for research into obesity and oestrogen-sensitive breast cancer

Obesity is a known risk factor for several cancers, including oestrogen-sensitive breast cancer after menopause. One possible explanation is that adipose tissue around the breast not only stores energy but also produces hormones and signalling molecules that can influence cancer cell growth.

– Being overweight can increase the risk of breast cancer after menopause, partly because adipose tissue produces oestrogen and other signals that can stimulate tumour growth, says Jan Frystyk, professor at the Department of Clinical Research, University of Southern Denmark, and the Department of Endocrinology M, Odense University Hospital, and one of the project leaders.

With the grant of DKK 11,990,000, Jan Frystyk and Professor Henrik Ditzel, Department of Molecular Medicine and Department of Clinical Research, University of Southern Denmark, and the Department of Oncology R, Odense University Hospital, will investigate the biological mechanisms – the processes inside cells – that link adipose tissue and oestrogen-sensitive breast cancer.

Why does obesity increase the risk of breast cancer?

After menopause, adipose tissue becomes an important source of oestrogen. Oestrogen can stimulate the growth of so-called oestrogen-sensitive (oestrogen receptor-positive) breast cancer, where cancer cells respond to the hormone.

Adipose tissue also releases a range of signalling molecules that affect the environment around a tumour. This can influence the signals in cells that determine whether cancer cells grow or are inhibited.

The researchers will investigate how this communication between fat cells and cancer cells takes place at the molecular level – and what role the protein STC2 plays in the process.

STC2 – a protein with a dual role in breast cancer

The project focuses on the protein stanniocalcin-2 (STC2), which is produced in several tissues, including adipose tissue, and plays a role in the communication between fat cells and cancer cells.

In many obesity-related cancers, high levels of STC2 are associated with a poorer prognosis. However, the picture appears to be different in oestrogen-sensitive breast cancer.

– In most cancers, STC2 appears to help tumours grow, but in oestrogen-sensitive breast cancer the data suggest that the protein may actually slow the disease, explains Rikke Hjortebjerg, assistant professor at the Department of Clinical Research and a researcher on the project.

The researchers will therefore investigate how STC2 influences the interaction between adipose tissue and tumour tissue, and how the protein is involved in the signalling pathways that regulate cancer cell growth.

The study will be based on tissue samples from women with oestrogen-sensitive breast cancer and will use advanced laboratory models.

– This includes so-called organoids – small, three-dimensional models of tumour tissue grown in the laboratory – as well as mouse models that closely mimic the disease, says Henrik Ditzel, the project’s second leader.

– We want to understand how STC2 sometimes behaves like a friend and at other times like an enemy – and whether we can learn to use it as a natural defence against cancer, says Rikke Hjortebjerg.

Can the research lead to more targeted treatment?

A better understanding of STC2’s dual role may, in the longer term, pave the way for new treatment strategies. If researchers can identify what regulates the protein’s activity, it could form the basis for more targeted treatment of oestrogen-sensitive breast cancer.

For women who are overweight and have breast cancer, the research may contribute to a more nuanced understanding of how adipose tissue affects the development of the disease. The perspective also extends beyond breast cancer, as obesity increases the risk of many common cancers.

The project is part of the research consortium Molecular Mechanisms Linking Obesity and Cancer (MMLOC), which also includes two other research projects and aims to strengthen understanding of the biological mechanisms linking obesity and cancer.

With the grant, the researchers will be able to investigate the interaction between adipose tissue and cancer in greater depth. In the longer term, the results may contribute to a more precise understanding of how obesity affects cancer – and whether the body’s own signalling molecules in some cases can be turned from a risk factor into part of the solution.