New discoveries about how arteries and lymph vessels develop in the gut could lead to new treatments for lymphatic diseases and preventing cancer spread.
There are two main circulatory systems in the body: the cardiovascular system that circulates blood, and the lymphatic system that performs a number of functions, including the removal of interstitial fluid, the clear fluid that bathes and surrounds cells.
In the gut, the lymphatic system absorbs fat and transports it to the liver, which distributes fat throughout the body. It also helps to educate immune cells to recognize pathogens, and it serves as a channel through which colorectal tumor cells can escape and travel through the body.
In the journal Developmental Cell, researchers from Cornell University, Ithaca, NY, and the University of Southern California in Los Angeles, report for the first time how - in the growing embryo - arteries form to supply the looping gut and guide the development of the gut's lymphatic system.
This is the first study to implicate arteries as the drivers of gut lymphatic development.
For the last 100 years, scientists thought veins were the drivers of lymphatic development.
New findings about artery and lymph vessel formation in the gut
In the growing embryo, a master-regulator gene called Pitx2 controls the looping of the intestines and the counter-clockwise pattern of organ growth so everything fits correctly inside the body cavity.
In their study, where they observed the development of the gut in chickens and mice the researchers found Pitx2 is also involved in the development of arteries and lymphatic vessels, which only occurs on the left side of the developing gut.
In their report they explain how they found artery formation in the intestines begins during gut rotation and proceeds strictly on the left side, dependent on the Pitx2 target gene Cxcl12.
And, while the correct precursors for artery formation "are present on the right, they fail to form vessels and progressively emigrate," they note.
In addition, they found - to their surprise - that gut lymph vessels also begin in the left side and arise only after, and are dependent on, formation of arteries, "implicating arteries as drivers of gut lymphangiogenesis."
Findings could help prevent spread of cancer in the gut
The research team believes the findings open the door to studying a range of human diseases. For example, they could guide the manipulation of the development of the lymphatic system to yield insights into many lymphatic-related diseases.
The lymphatic system is currently the main place to look for signs of metastasis - where cancer is beginning to spread from the primary tumor to form secondary tumors in other parts of the body. So, if you can block these vessels in the vicinity of cancer, perhaps you can block the spread of cancer.
The majority of cancer deaths result from metastasis. In the case of colorectal cancer, secondary tumors usually occur in the liver, lung and peritoneum - the tissue that lines the abdominal wall and covers most of the organs in the abdomen.
According to the Centers for Disease Control and Prevention (CDC), of cancers that affect both men and women, colorectal cancer is the second leading cause of cancer-related deaths in the US.
In 2011 - the most recent year for which numbers are available - 135,260 people in the US were diagnosed with colorectal cancer and 51,783 people died of it.
Funds for the study came from the Cornell Center for Vertebrate Genomics, the National Institutes of Health and the March of Dimes.
References:
1. The left-right Pitx2 pathway drives organ-specific arterial and lymphatic development in the intestine, Aparna Mahadevan, et al.,Developmental Cell, doi:10.1016/j.devcel.2014.11.002, published online 4 December 2014, abstract.
2. Cornell University news release accessed 16 December 2014.
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