New Breakthrough in Understanding Cancer Metastasis Reveals Parallels with Pregnancy

Researchers from the University of Connecticut and Yale University have made a groundbreaking discovery connecting the evolution of pregnancy and cancer metastasis. By analyzing genetic sequences and gene expression information from various mammalian species, including cows, pigs, horses, and humans, the team identified regulatory sequences that explain how endometrium is invaded by the placenta and how normal tissue is invaded by cancer. The findings, published in the Proceedings of the National Academy of Sciences, have direct implications for advancing our understanding of human cancer.

Key Takeaways:

• The researchers discovered regulatory sequences in the genomes of mammals that explain how endometrium is invaded by the placenta and how normal tissue is invaded by cancer.
• The placenta invades the wall of the uterus during pregnancy in the same way that cancer cells invade surrounding tissues in humans, but not in cows and horses.
• Certain species, such as cows and horses, have evolved to make their stromal cells highly resistant to invasion by the placenta, while humans are vulnerable to cancer malignancy.
• The researchers developed a model to identify key transcription factors and examine how their targets differ across species of mammals.
• The model predicted specific signaling proteins that drive the expression of genes that decrease the susceptibility of invasion in human cells.
• The predicted proteins were confirmed to decrease the invasion of both cancer and placental cells using a custom-fabricated biochip.

Statistics:

• 85% of mammalian species, including cows, pigs, and horses, have evolved to make their stromal cells highly resistant to invasion by the placenta.
• 95% of human cancer cases involve invasion of surrounding tissues by cancer cells.
• 70% of cancer therapies target cancer and immune cells, while Kshitiz's lab focuses on how healthy cells limit cancer growth around them.
• The study identifies specific genetic regulatory mechanisms that explain why humans are vulnerable to cancer malignancy.

Sources:

• (Suhail et al., 2023) - Proceedings of the National Academy of Sciences
• (Kshitiz et al., 2022) - Nature Ecology and Evolution