Outcompeting Cancer Now a Reality

Outcompeting cancer cells by normal, healthy body cells in the struggle for survival, has become a reality, reveals a new study by researchers at the Champalimaud Center for the Unknown in Lisbon, Portugal. The reason behind why cancer cells are able to outwit normal body cells in the fight for survival is that they are themselves also human cells. As a result, these cancer cells are not only capable of subverting the body’s immune defenses, but also highjacking them, when the need arises.

The study was led by Dr. Eduardo Moreno, Ph.D, who is a Principal Investigator at the Champalimaud Center for the Unknown in Lisbon, Portugal. He has discovered a cell-competition mechanism, which he has termed ‘fitness fingerprints’. This ‘fitness fingerprint’ mechanism was first discovered in the fruit fly (Drosophila melanogaster) in 2010 by Moreno’s group.

The present study, published in Nature, has established that the same mechanism also exists in humans. Moreover, by blocking this mechanism, the proliferation of the cancer cells can be stopped.

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Study Findings

• The gene that codes for ‘fitness fingerprints’ was identified in the human genome
• The gene coded for four different types of ‘fitness fingerprints’, including two types of Win ‘fitness fingerprints’ and two types of Lose ‘fitness fingerprints’
• The Win ‘fitness fingerprints’ indicated that the cells were young and healthy
• The Lose ‘fitness fingerprints’ indicated that the cells were old or damaged
• The impact of the Win and Lose ‘fitness fingerprints’ on cancer growth was evaluated by studying their expression patterns in the following four types of tissues:
• Malignant tumors – Breast and colon
• Benign tumors – Breast and colon
• Tissue adjacent to the tumors
• Normal tissue
• Expression of Win was less in normal tissue, while expression of Lose was even lesser
• Expression of Win was significantly elevated in all cancer tissues, with more in malignant tumors than benign tumors
• Expression of Lose was significantly higher in tissue adjacent to tumors, compared to normal tissue
• Expression of Lose was significantly higher in tissue adjacent to malignant tumors, compared to benign tumors
• Expression levels of Win in tumors and Lose in adjacent tissues, accurately predicted cancer malignancy 86.3 percent of the time

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Interpretation of the Study Findings

The findings indicate that neighboring cells in the human body continuously monitor each other’s activity and level of fitness through the two types of fitness markers identified on their surface, namely, Win and Lose.

If a cell is less fit than its neighboring cells, meaning that it expresses less Win and more Lose, then the neighboring cells eliminate it, thereby ensuring that the tissue as a whole remains healthy. This mechanism is important for the following biological processes:

• Normal growth and development
• Regeneration of tissues following injury
• Prevention of premature aging

However, this same mechanism can be highjacked, leading to the development of cancer. In this context, Moreno says:“Cancer cells use these ‘fitness fingerprints’ to disguise themselves as super-fit cells by expressing relatively many more Win ‘fitness fingerprints’ on their surface than their healthy neighbors. This makes the normal cells that surround cancer cells appear less healthy by comparison. In this way, cancer cells trick their healthy neighbors and bring about their death, consequently destroying the tissue and making room for tumor expansion."

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Investigation of Potential Therapeutic Applications

The study findings indicated that high expression of Win in tumor tissue and high expression of Lose in adjacent tissue was an essential requirement for the growth and expansion of the tumors. Based on these findings, the potential therapeutic applications were investigated as follows:

• The above mechanism was blocked by knocking out the Win/Lose fingerprints in human tumor tissue, transplanted in mice
• This led to a reduction in tumor size, indicating that the aggressiveness of the cancer cells towards adjacent host cells was significantly decreased
• In an attempt to further increase the therapeutic potential, the blocking of Win/Lose expression was combined with chemotherapy
• This led to a further reduction in tumor size and in some cases, complete elimination of the tumors

Future Plans

The research team plans to conduct a more detailed study of the mechanism associated with the expression of Win/Lose ‘fitness fingerprints’ and its effect on cancer. They also plan to develop a new type of cancer drug in collaboration with clinicians.

Concluding Remarks

Moreno indicates that the present study was based on purely curiosity-based research that led to a discovery having benefits for human health. In this regard, he says: “When we began studying cell competition in the fruit fly, we were addressing it as a basic biology question: how do tissues eliminate viable, but suboptimal cells. From there to potential cancer therapies seems like an almost unlikely development, but this is how research works; you start with the curiosity to know how things work and from there, sometimes, you find yourself on the road to potential novel therapies.”

He concludes: “These findings are very encouraging, but they are still preliminary and it will be some years before we are able to use them to help cancer patients.”

Funding Source

The study was funded by multiple organizations. Some of these include the European Research Council, the Swiss National Science Foundation, the Josef Steiner Cancer Research Foundation, the Champalimaud Foundation, and the Swiss Cancer League, among others.

Reference:

1. Flower Isoforms Promote Competitive Growth in Cancer - (https://doi.org/10.1038/s41586-019-1429-3)

Source-Medindia