FINDMETASTASIS

In vivo studies and screens for new factors that promote or suppress tumor metastasis

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 Obiettivo del progetto (Objective)

'Metastasis is the process whereby a primary tumor (usually highly malignant in nature) spreads to distant locations in the body. Understanding step-by-step how particular confined tumors acquire invasiveness and/or spreading potential is a scientific challenge that can help us to develop new strategies for metastatic cancer prevention or treatment. In mouse models and in humans, the inactivation of the E-cadherin gene and the activation of genes of the SNAIL family are markers of the initiation of metastasis from epithelial tumors – a process that is called epithelial-mesenchimal transition, and that is similar, albeit not identical, to what occurs during normal development. In vivo, however, neither the activation of E-cadherin nor the activation of SNAIL genes is sufficient to trigger malignant transformation, indicating that additional unknown factors are required for this process to take place. Our project has as its main objective to develop and explore genetically traceable animal models that recapitulate the initial steps in malignant transformation of tumorous growth in vivo. With these animal models we intend to understand the molecular mechanisms that activate (or inactivate) genes that trigger metastasis and that convert a stationary eptithelial cell into an invasive one (ie, one with the capacity to invade and degrade the basal lamina). We hope that these models will help to open new fields of investigation to isolate new potential targets for therapeutic intervention.'

Introduzione (Teaser)

Several genes, proteins and mechanisms have been implicated in activating or inactivating tumours. New treatments for cancer may be next.

Descrizione progetto (Article)

Tumours are growths that form on or in the body, and can be benign or malignant in nature. Primary tumours are usually highly malignant and can spread to others locations in the body. A close understanding of how they become invasive and metastasise (spread) in the body can help develop treatment for serious cancers.

Generally, metastatic tumours can be diagnosed when specific genes in the body become inactivated and others are activated. However, live testing in mice and humans has shown that manipulating these specific genes did not trigger malignant transformation. This indicated that additional unknown factors are required for this process to take place.

The Findmetastasis project, funded wholly by the EU, recently explored animal models that traced the steps in malignant transformation of tumours. Its aim was to conduct in vivo (laboratory) studies to screen for new factors that promote or suppress tumour metastasis.

A good place to start looking for these factors was in drosophila, the common fruit fly. Hallmarks of cancer such as over growth, evading programmed cell death, tissue invasion and metastasis have been found in tumorous eye tissues of drosophila. This provided a powerful experimental model for the genetic dissection of tissue homeostasis, growth and cancer in vivo.

The project team managed to partly unravel the molecular steps involved in drosophila eye tumours and how they could be triggered. Several very specific mechanisms have been identified at a molecular level, including a gene in drosophila that can act as a tumour suppressor. Specific proteins were also implicated in tumour-related activity, in addition to other mechanisms related to gene formation.

Together, these findings are considered very important in bringing the medical research community closer to understanding metastatic tumours and embarking on a quest for a cure. Positive results in this respect may be just a few years away.