Integrin expression by tumor exosomes could help oncologists pinpoint which patients will present with metastatic disease – and to which organs
Roisin McGuigan |
The ability to predict which patients will develop metastatic disease, and where, would undoubtedly be a huge coup for oncology – but much of metastasis still remains a mystery. A common theory is that tumor cells dictate metastasis, but a recent study published in Nature, shows that this may be a misconception.
“Tumor cells only indirectly influence metastasis. The tumors are excreting exosomes, and these are preparing future sites of metastasis, not the cells, so this is very different from the accepted dogma,” says co-author of the Nature paper (1), David Lyden.
Lyden and his colleagues found that tumor-excreted exosomes have distinct expression patterns of integrins, and it appears that the exosomes prepare organs to host tumor cells, by causing responses such as inflammation and vascularization, forming a metastatic niche (see Figures 1 and 2). They looked at 10 tumor cell lines which usually metastasize to specific organs – for example, pancreatic cancer often spreads to the liver – and analyzed the proteins being expressed by the cancer exosomes. Analysis showed that they could link the expression of different integrin proteins with metastatic disease in the lung, liver and brain (see Table 1).
|ITGα 6, ITGβ 4, and ITGβ 1||Lung Metastasis|
|ITGβ 5||Liver Metastasis|
|ITGβ 3||Brain Metastasis|
Now, the team plan to continue their research in a larger study group, looking at different organs, and different patients, in order to further understand how metastasis works. They have a particular interest in bone cancer, as they found that patients with this secondary cancer had no integrin expression.
“Our work illustrates that we can now do a very easy blood test and predict who will develop metastatic disease, and importantly to what organ they will metastasis to. So this is really changing our traditional way of treating metastasis. We can potentially start treatment much earlier, and make a bigger impact,” says Lyden.
“This study could in the future also be applied to be used for follow-up of the patients after surgery or chemotherapy. Importantly, our work shows that preparation of future metastasis sites by the exosomes starts long before the cancer cells arrive – they indicate the true start of metastasis,” adds the study’s first author, Ayuko Hoshino.
- A Hoshino et al., “Tumor exosome integrins determine organotropic metastasis”, Nature, 527, 329–335 (2015). PMID: 26524530.