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In many mammals, including humans, the placenta invades the uterine wall during pregnancy in the same way that cancer cells invade surrounding tissue
.
An animal study by researchers at Connecticut Health University and Yale University has led to new advances in the evolution of pregnancy and cancer metastasis
Their research was published in the Proceedings of the National Academy of Sciences
.
The researchers write: "Among eutherian (placental) mammals, the placenta embedded in the maternal endometrium exhibits dramatic variation, ranging from deeply invasive (as in humans) to non-invasive (as in cattle)
.
The placenta nourishes.
Dr.
Yasir Suhail, along with Dr.
Kshitiz, assistant professor in the Department of Biomedical Engineering, discovered regulatory sequences in the genomes of mammals, including cows, pigs, horses, and humans, that explain how the endometrium is invaded by the placenta, and how normal How tissue is invaded by cancer
.
"When you look at the picture of the placenta, it looks strikingly similar to cancer in other parts of the body," Kshitiz said.
"
Even the molecular mechanisms are very similar
.
This is very different from the situation in cows and horses, where the placenta does not Invading the mother
The researchers looked at endometrial cells from different species and found that in order to resist invasion of the placenta, some species have evolved over time to make their mesenchymal cells -- the connective tissue cells in the organ -- highly resistant to any invasion
.
"Our new framework identifies key transcription factors and studies how their targets differ from cattle, pigs, horses and humans," Suhail said
.
"What we learn from other species can be directly applied to advance our understanding of human cancer
Suhail uses genome sequence and gene expression information to predict specific signaling proteins that drive gene expression and reduce susceptibility to human cell invasion
.
Using a custom-built biochip, the researchers were able to confirm that these predicted proteins did reduce cancer and placental cell invasion
"We all think that human cancers are the result of the cancer cells themselves
.
But what we propose is that mammals have very different mechanisms to resist the spread of cancer that have actually been derived to resist fetal intrusion into the mother's body," Kshitiz said
While other researchers target cancer and immune cells, Kshitiz's approach could help change the way cancer is usually treated
.
"This study identifies specific gene regulatory mechanisms that explain these differences and points us in many directions for rethinking anti-cancer treatments, from those that kill cancer to creating new ones that 'check' cancer within its reach
.
"
Tracing the cis-regulatory changes underlying the endometrial control of placental invasion
