metastasis, breast cancer, metastatic niche, tumor microenvironment

Metastasis Biology

Metastatic organotropism and tracing cancer-metastatic niche interactions

Metastasis is a process whereby some cancer cells leave the primary site, travel and survive in the circulation and eventually successfully colonise distant organs. Although cancers detected before metastatic spread often have favourable outcomes owing to resectability and interventions such as radiation, chemotherapy and novel therapeutics, the presence of distant metastases is associated with markedly worse survival (1). Despite this, most current therapies act systemically and are typically tailored to the molecular profile of the primary tumour, regardless of the metastatic pattern of patients (2). Cancer cells display metastatic tropism, i.e. tendencies to colonise specific organs. As such, the metastatic pattern varies between cancer types and subtypes. For instance, prostate cancer shows preferential colonisation of the bone. Breast cancer, which is the most common malignancy in women (3), typically metastasizes to the bone, liver, lungs and brain. Furthermore, the subtypes of breast cancer, characterised by the expression of hormone receptors oestrogen (ER), progesterone (PR) and human epidermal growth factor receptor 2 (HER2), are associated with different metastatic patterns, disease progression and response to therapy (4). Triple negative (TN) breast cancer shows a tendency to colonise visceral organs such as liver and lungs, while ER+ patients more commonly develop bone metastases. Crucially, we have shown how the site to which cancer cells have metastasised shapes their behaviour and metastatic properties priming or supressing them for further spread (5). Our lab aims to elucidate the mechanisms of organotropism, and the dynamic crosstalk between cancer and site-specific metastatic niches, to understand how they contribute to secondary metastasis-to-metastasis seeding and disease progression. We track tumour cells across the metastatic cascade using lineage-tracing tools, imaging, and microfluidic isolation, integrated with molecular and computational analyses. Using patient samples and in vivo models, we aim to pinpoint actionable points for therapeutic intervention in cancer - niche interactions.

1. A. W. Lambert, D. R. Pattabiraman, R. A. Weinberg, Emerging Biological Principles of Metastasis. Cell 168, 670–691 (2017). 

2. T.-A. Moo, R. Sanford, C. Dang, M. Morrow, Overview of Breast Cancer Therapy. PET Clinics 13, 339–354 (2018). 

3. H. Sung, J. Ferlay, R. L. Siegel, M. Laversanne, I. Soerjomataram, A. Jemal, F. Bray, Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA A Cancer J Clinicians 71, 209–249 (2021). 

4. L. Gerratana, V. Fanotto, M. Bonotto, S. Bolzonello, A. M. Minisini, G. Fasola, F. Puglisi, Pattern of metastasis and outcome in patients with breast cancer. Clin Exp Metastasis 32, 125–133 (2015). 

5. M. K. Sznurkowska, F. Castro-Giner, Y. Zhang, A. Ring, F. D. Schwab, F. Albrecht, K. D. Mertz, K. Strittmatter, L. L. Ozimski, S. Budinjas, G. Auray, C. Giachino, V. Taylor, A. Gvozdenovic, I. Malanchi, H. Frauchiger-Heuer, A. Wicki, M. Vetter, N. Aceto, Mapping the niche of breast cancer metastases in lung and liver. (2024). https://doi.org/10.1101/2024.10.04.616491.