Discovery of widespread tumour growth gene holds promise for cancer treatment

22 Sep 2007
A new and promising target for anti-tumour therapy has been found by Italian scientists at the University of Cheiti Foundation (CESI). The team, working under Professor Saverio Alberti, found a widespread mechanism for the stimulation of tumour growth, a discovery which is already leading to the development of novel diagnostic and therapeutic procedures.

The function of the Trop-2 gene, previously a mystery, was found to be influencing a cell to convert one kind of signal or stimulus into another. The gene was known for its role in the growth of human embryos and so was investigated for its part in another invasive function, tumour growth.

Analysing the genes in human tumours, the scientists found Trop-2 in the vast majority, for example, breast, colon, stomach, lung, prostate, ovary, cervix and pancreas. The gene was found to be over-expressed in 74% of the tumour types analysed. "This figure is high", stated Professer Alberti: "In comparison, telomerase over-expression, possibly the most fundamental mechanism for cell immortalisation, is observed in 80% of all tumours."

The study of the 1755 tumours was carried out by DNA array, Serial analysis of gene expression (SAGE) and immunohistochemical (IHC) analysis. IHC looks at the interaction of antibodies and antigens in tissues, and has the advantage of showing exactly where a given protein is located. This allowed the scientists to develop anti Trop-2 monoclonal antibodies for immunotherapy; potentially adjusting the human immune system to reject and destroy Trop-2 expressing tumours.

Not only was the gene found to be over expressed in many tumours, it was also found to be a unique marker of cancer metaseses (spread) in various tumours. The team found that there were higher levels of Trop-2 in secondary tumours than primary. Trop-2 induces these metastases through mechanisms that the scientists are beginning to unravel. The most intriguing of the findings, they say, is the presence of two sequence elements in the area of the gene which controls its function. These control the likelihood of the cancer's spread, so may be key to the identification of signalling molecules that promote or inhibit the formation of metastases. "If we can identify such molecules we will be approaching a situation where we could influence their activity and hence either encourage or prevent it" said Professor Alberti. "This could be an important step towards stopping cancer in its tracks"