Cells, like every other system, need to keep their insides clean in order to stay healthy and function properly. One of the ways by which this is accomplished is by discarding their ‘trash’ via a mechanism called exocytosis. In simple words, this means that the cells basically just ‘throw out’ their trash in ‘garbage bags’ called exosomes. Exosomes are membrane-bound organelles or packages that contain DNA, RNA and protein trash that cells want to get rid of. Once out of the cells, the exosomes can break open, or form a rubbish heap like a landfill.
It is already a known fact that cancer cells produce more exosomes than normal healthy cells. Now, in an attempt to study the effect of these exosomes produced by cancer cells, researchers at the University of Texas MD Anderson Cancer Center, have stumbled across the intriguing possibility that cancer cell exosomes may be able to ‘infect’ their neighboring healthy cells and turn them into cancerous ones.
So how do healthy exosomes differ from cancer exosomes?
This question was the first one researchers strived to answer in a study published recently in Cancer Cell, by looking more closely at the exosomes produced by cancer cells and comparing them to those from normal healthy cells.
Experimentally, the scientists isolated exosomes from human and mouse healthy mammary cells (controls) and four different types of breast cancer cells, metastatic and nonmetastatic, that had been grown in culture. Considering the fact that exosomes contain mostly cellular trash like DNA, RNA and proteins, the scientists then compared the contents of the two, healthy and cancer exosomes. Intruigingly, they found that the cancer exosomes were significantly enriched in the components required to produce small noncoding RNAs that can regulate gene expression, termed microRNAs (miRNAS). Even more fascinating was the fact that exosomes produced by metastatic cancer cells showed higher enrichment in miRNAs than those derived from nonmetastatic cancer cells.
Since miRNAs can control gene expression can cancer exosomes affect gene expression in nearby healthy cells?
Because of the gene expression silencing potential of miRNAs the researchers were prompted to examine the effect of cancer exosomes on healthy noncancerous cell gene expression. Surprisingly, incubating healthy cells with cancer exosomes led to an altered miRNA expression profile, but also altered global gene expression in the healthy cells, suggesting that the cancer exosome miRNAs are able to enter the healthy cells and regulate their gene expression.
So if cancer exosomes can alter healthy cell gene expression can they also lead to tumor formation?
The answer to this question seems to be ‘YES’. When researchers injected healthy cells that had been previously exposed to cancer exosomes, into mice mammary fat pads, they observed tumor formation in these mice. To examine if this effect was due to the miRNAs in the cancer exosomes, the scientists then disabled the miRNA producing machinery by blocking Dicer, a protein that is required in order to produce mature functioning miRNAs, in the cancer cell exosomes. Incubating the healthy cells with these ‘altered’ cancer cell exosomes before injecting them into mice, led to reduced tumor formation, thus providing evidence for the exosome miRNA implication in oncogenesis.
To further prove their point and test their results in human patients, scientists also collected exosomes from 11 breast cancer patients and tested their ‘oncogenic potential’ when coinjecting them into mice together with normal healthy cells. 5 out of 11 samples of exosomes isolated from breast cancer patients led to tumor formation, whereas there was no tumor formation in any of the mice injected with exosome samples collected from healthy patients.
How can cancer exosomes be exploited to benefit cancer patients?
According to scientists, this still seems to be a difficult question to tackle. Blocking exosomes in general to slow cancer and prevent it from spreading is difficult and controversial, since this would also block exosomes from healthy cells. Blocking healthy cell exosomes is an unwanted effect, since it has been shown that exosomes from healthy cells contain proteins that may help prevent cancer. Finding a way to specifically block exosomes only from cancer cells could potentially be beneficial for cancer patient treatment.
Another way to take advantage of the newly acquired information about cancer cell exosomes would be to use them as a marker to monitor cancer and its progression. Since exosomes are a lot easier to isolate from blood than tumor cells and there seem to be great numbers of them made by each cell, it would be a lot easier to use them to track this disease, providing us with a mighty tool in cancer progression detection.
Melo, S. A. et al. Cancer Cell (2014)
Logozzi, M. et al. PLoS ONE (2009)
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Article last time updated on 20.11.2014.