Evolutionary connection between pregnancy and cancer metastasis

Kshitiz, assistant professor in the department of biomedical engineering -- a shared department between the School of Dental Medicine, School of Medicine, and School of Engineering -- and Gunter Wagner and Andre Levchenko at Yale University used evolutionary biology to draw the connection in the Nature Ecology & Evolution journal.

In many mammals, the placenta invades the wall of the uterus during pregnancy in the same way that cancer cells invade surrounding tissues. In other mammals -- including cows, pigs, and horses -- the placenta does not invade as aggressively. Interestingly, in these mammals, tumors rarely metastasize or spread.

Looking at cells from endometrium of various species, Kshitiz found that in order to resist invasion of the placenta, certain species have evolved over time to make their stromal cells -- the connective tissue cells in an organ -- highly resistant to any invasion. In contrast, humans are particularly vulnerable to cancer metastasis owing to their highly invasive placentation during pregnancy. This study identified the cause linking the curious similarity between pregnancy and cancer invasion across various mammals.

"This work fundamentally changes the way we look at cancer metastasis," said Kshitiz. "Basically, it puts stromal cells at the center of invasion associated with cancer and pregnancy, correlating the two. Who thought that pregnancy and cancer are so similar, and pregnancy in some ways is just controlled invasion?"

Kshitiz continues, "In humans, unfortunately, the invasion in pregnancy as well as by cancer is much less controlled. Interestingly, there are mammals where both pregnancy and cancer malignancy are highly controlled, and now we know why. These mammals (the two hoofed animals: cows, horses, pigs, etc.) have evolved their barrier to invasion."

Kshitiz, Wagner, and Levchenko's research has unveiled the exact genes which are different in the supportive stromal tissue between humans and these animals, opening an entirely new field of changing the stromal surrounding of cancer to limit cancer invasion in a guided way.

The findings can revolutionize our way of thinking about cancer metastasis and allow development of new therapeutics. Making human cells similar to cow cells, for instance, could potentially make humans more resistant to the spread of cancer.

The collaborators are members of the Cancer Systems Biology at Yale program, funded by the National Cancer Institute U54 Center Grant for Cancer Systems Biology: U54-CA209992-Project 2.