Unravelling cancer invasion

In many aspects, cancer biology has many features resembling developmental processes such as cell migration. Invasion represents a fundamental step in tumour progression and is the main driving force for metastasis and cancer-related mortality. Accumulating evidence indicates that similar to the early stages in development, cancer cells of many epithelial and mesenchymal tumours also invade in a collective manner.

The detailed mechanisms and molecular determinants of this collective invasion model are poorly understood. To shed light into this phenomenon, the EU-funded CICCI project investigated the role of chemokines and their receptors. Chemokines are small signalling proteins usually implicated in immune responses that also enhance cancer progression. However, the majority of existing data on the role of chemokines has been obtained at the single cell level. Researchers wished to extend these findings in vivo in mouse and zebrafish models.

To this end, they performed extensive expression analysis in fibrosarcoma and squamous cell carcinoma cells from head and neck tumours in three-dimensional invasion cultures. Key chemokine molecules and their receptors were identified and validated through in vitro inhibition or overexpression experiments. Additionally, orthotopic tumour xenografts in nude mice were performed to evaluate the role of chemokines in vivo.

Overall, the CICCI project provided vital information on the role of chemokines on collective cancer invasion in vivo. Understanding the mechanisms that drive cancer cell metastasis could unveil potential therapeutic targets against cancer.