How metastasising cancer cells invade organs
The mechanism discovered will yield a completely new approach for the development of drugs to combat metastasis
- Date : 18 Jul 2012
- Topic : Gastrointestinal cancers
It is not primary tumours that are responsible for the majority of cancer deaths, but rather their metastases. Physiologists and neuropathologists from the University of Zurich have now identified the origin of metastasis formation, thereby becoming the first to reveal the pathway of metastasising intestinal cancer cells out of the blood stream. The results allow new approaches in the development of cancer therapies.
Thanks to more effective therapy and better early detection, primary tumours are only responsible for 10% of cancer deaths in industrial nations. Nowadays, the vast majority die from the consequences of metastasis. Until now, the actual reason for the metastatic spread in certain organs was unknown, and it was unclear as to how the secondary cells were able to enter the tissue of other organs from the bloodstream.
Now, researchers have identified the mechanism that helps metastasising intestinal cancer cells to infiltrate the organs from the blood vessels. Lubor Borsig and Mathias Heikenwalder's team demonstrate that cancer cells manipulate specific "doorman receptors" on the endothelium of the blood vessels.
Tumour cells manipulate blood-vessel doorman
Chemokines play a key role in the immune system. Tumour cells are also capable of producing chemokines and mobilising the body's own special immune cells, monocytes. Consequently, elevated levels of the tumour's own chemokine CCL2 are characteristic of metastasising breast, prostate and bowel cancer. Until now, high CCL2 values were primarily taken as an indication of strong tumour growth and a poor prognosis for the disease. Based on in-vivo and in-vitro experiments on lab mice, Borsig and Heikenwälder show that CCL2 is far more than an indicator of the cancer's aggressiveness. CCL2 activates a doorman receptor and enables cancer cell to leave the blood circulation and metastasise in other organs, according to Borsig. The role of the doorman detected on the endothelium for the first time and referred to as CCR2 in a healthy organism is not known. The researchers suspect that the doorman modulates the permeability of the blood vessels during the body's immune response.
New approach for drug development
The researchers are convinced that the mechanism discovered will yield a completely new approach for the development of drugs to combat metastasis in breast, prostate and bowel cancer. Suppressing the tumour's chemokine expression or blocking the doorman for the tumour chemokine to inhibit more cancer cells from entering healthy tissue from the bloodstream is conceivable.
Caption image 1:
This is an electron microscopy from a tumour cell that is on the way to extravasate through an alveolar endothelium blood capillaries – the tumour cell is depicted in blue green, the endothelial cell in purple red. The protrusion of the tumour cell are seen that form their way through the endothelial cell.
Caption image 2:
Tumour cells (green) adhere on the endothelium (red) that gets activated and permeable through CCL2-CCR2 signaling. Tumour cell extravasation is facilitated by recruited monocytic cells (blue). Technique: Adaptation of confocal image stacks creating an artificial surface.
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