How to make a lung

Washington, Aug 18 (ANI): Scientists from University of Pennsylvania have shed light on how lungs are developed in the body.

They have identified a tissue-repair-and-regeneration pathway in the human body, including wound healing that is essential for the early lung to develop properly.

The researchers have also discovered two molecules in this pathway, Wnt2 and Wnt2b that play a key role in early lung development.

“We wanted to know the answer to a seemingly simple question: What is required to generate the lung in mammals?” said senior author Dr Edward Morrisey, Associate Professor of Medicine and Cell and Developmental Biology at the University of Pennsylvania School of Medicine.

“Wnt molecules are important for lung growth and we think that some of the molecules in the Wnt pathway are needed to specify lung progenitor cells and if not enough cells are ‘told’ to make a lung, an animal develops a faulty, smaller organ or even no lung,” he added.

Understanding how a lung develops is important in treating or preventing a host of lung and pulmonary diseases in children.

In the developing embryo, the lung, pancreas, liver, thyroid, and stomach all come from the foregut region, which starts out looking like a long tube.

“These organs bud from this undifferentiated tube and go on to develop into specific tissue types. The lung is one of the last to bud off the foregut during development,” said Morrisey.

The team focused on the Wnt pathway to see where and when Wnt molecules were expressed along the foregut tube, even before the lung starts to become a recognizable organ.

They found that the Wnt proteins Wnt2 and Wnt2b are expressed in the cells surrounding the foregut, right where the lung will eventually form. When they are knocked out, the animals completely lacked lungs.

Morrisey surmised that Wnt2 and Wnt2b were required to specify the early progenitors for the lung in the foregut.

The Morrisey lab showed that activation of the Wnt pathway resulted in formation of lung progenitors in both the esophagus and stomach where they are normally excluded.

“The ability of Wnt to program esophagus and stomach endoderm to a lung fate points to the critical role this pathway plays in lung development and suggests the possible use of Wnt in generating lung epithelium from non-lung sources,” said Morrisey.

The findings are described this week in Developmental Cell. (ANI)

What prompts lung cancer to spread

Washington, July 3 (ANI): Researchers from Memorial Sloan-Kettering Cancer Centre claim to have identified a cellular pathway that is involved in spread of lung cancer.

It is the same cellular pathway that has been shown to be involved with the spread of colorectal cancer, say the researchers.

The pathway enhances lung cancer’s ability to infiltrate and colonize other organs without delay.

Using bioinformatics, the researchers analysed large collection of lung tumour samples.

They found that the WNT cell-signalling pathway was the only one out of the six pathways tested that was hyperactive in lung tumours that went on to metastasise, and was normal in those that did not spread.

They also observed that WNT hyperactivity was associated with aggressive biological tumour characteristics and poor clinical outcome, suggesting that cancer metastasis was linked with poor survival.

“Mutations that activate the WNT pathway are a common cause of colon cancer, but lung tumors are initiated by mutations in other genes so we were surprised that a hyperactive WNT pathway would be responsible for metastasis in lung cancer,” said the study’s senior author Dr Joan Massague, Chair of the Cancer Biology and Genetics Program at MSKCC and a Howard Hughes Medical Institute investigator.

“Our findings suggest that using treatments that target the WNT pathway may help prevent lung cancer from repeatedly seeding itself throughout the vital organs of patients at risk for metastasis,” she added.

The study has been published online in the journal Cell. (ANI)