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Error Switch
The enzyme that helps cancer cells wreak
havoc has been pinned down, reports Biplab Das
Normal cells are endowed with a unique switch that tells them precisely when to start and stop dividing. But cancer cells are robbed of this faculty and forget to put brakes on their growth. What is more, these eccentric cells migrate to new sites inside the body and initiate uncontrolled cell growth - called metastasis - at a global scale.
An enzyme that has long been suspected to trigger abnormal cell growth has finally been pinned down by cancer researchers. In the July issue of
Nature Medicine, two research teams, one led by Christopher Parish of the John Curtin School of Medical Research
(JCSMR) in Canberra, Australia, supported by Progen Industries in Brisbane and the other by Israel Vlodavsky at Hadassah, Hebren University in Jerusalem helped by Iris Pecker of the Insight Ltd,
Rehovot, Israel, report to have identified the enzyme called
heparanase.
They have also homed in on the gene that encodes the enzyme. According to the researchers, inhibiting the enzyme's action may be the key component of cancer therapy. As cancer cells roam the body, they dismantle the meshwork that holds the cells together. The meshwork mostly consists of carbohydrate
heparan sulphate that is snipped off by heparanase.
Previous studies have shown enzymes called proteases cause cellular architecture to collapse. The latest discovery indicates that only heparanase is responsible for metastatic growth of cancer cells.
To maintain this unbridled growth, cancer cells need unending source of
nourishment which is met by constant growth of new blood vessels. It has been found that heparanase aids the growth of new blood vessels around the cancer cells.
To make heparanase a potential drug target, researchers needed to purify the enzyme to know its true nature. Initially, enzyme's fragility stymied their effort. But, the Israeli group purified heparanase from a human liver cancer cell line and also from human placenta.
At the same time, JCSMR group got it from human platelets. At first, both groups deciphered amino acid sequences of the enzyme. Having
known the amino acid sequences, they traced the gene that codes for
heparanase, and cloned it. Now, Vlodavsky introduced a copy of the gene into a
non-metastatic mouse melanoma and lymphoma cancer cells. By adding the gene turned the mouse melanoma and lymphoma cancer cells malignant. Meanwhile, Parish reports to have found
heparanase-inhibitor called PI88, which reduced the number of lung
tumours, formed by injected breast cancer cells, in rats by 90 per cent.
This inhibitor also deprived the tumours of blood supply diminishing the growth by half. Inspired by the encouraging results from animals, researchers now plan to pursue experiments in humans.
Proegen has already undertaken test to know the inhibitor's safety in healthy volunteers. In future successful trials in cancer patients may give us the first deadly arsenal in our armoury against cancer.
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