'An important step towards stopping cancer in its tracks'

Italian researchers have found a mechanism for the stimulation of tumour growth in humans. This discovery will lead to the development of novel diagnostic and therapeutic procedures, the
scientists explained at the European Cancer Conference in Barcelona.

The team from the University of Chieti Foundation (CESI) disclosed the function of the Trop-2 gene, a product of the TACTD2 gene, which is expressed in the placenta, an ‘invasive’ normal
tissue. ‘The function of Trop-2 was a mystery until now,’ said Professor Saverio Alberti from CESI, ‘but knowing its expression in the trophoblast during pregnancy, we thought that it might
well be involved in another invasive function – tumour growth.’ Trophoblasts are cells forming the outer layer of the blastocyst – a stage of human development early in pregnancy. They provide
nutrients to the embryo and develop into a large part of the placenta.

When the scientists analysed the genes in human tumours, they discovered that Trop-2 was expressed in the vast majority of them, including those in the breast, colon, stomach, lung, prostate,
ovary, endometrium, uterine cervix and pancreas. On average, Trop-2 over-expression was found in 74% of tumours examined. Most other markers will either show lower figures or can only be
detected at high frequency in a subgroup of tumours.

‘Trop-2 is also a unique marker of cancer metastases in different tumour types – including colon, stomach, breast and ovary – and across a number of species,’ Professor Alberti went on to
explain. The research revealed that most metastases in lymph nodes or down-stream organs, for instance the liver in colon cancer, express higher levels of Trop-2 compared with primary tumours.
Trop-2 induces these metastases.

Trop-2, however, also contains two specific sequence elements in its cytoplasmic tail, or its ‘signalling engine’. One of these elements acts as an enhancer of metastatic propensity, the other
as a silencer. ‘If we can identify such molecules, we will be approaching a situation where we could influence their activity,’ said Professor Alberti, indicating that this was the most
intriguing of the findings. ‘This could be an important step towards stopping cancer in its tracks.’

Additional research into how Trop-2 triggers receptor activation, which in turn results in cell change, will be the next step. ‘This will be crucial for the better understanding of the way in
which tumour growth is regulated by the gene and will also provide additional targets for anti-cancer drugs,’ Professor Alberti points out. ‘We are very excited about the prospects for therapy
which we can see arising from this discovery.’

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