Lymphatic Lines

Lymphatic vessels grow towards two chemokines, revealing signals that could be important in cancer metastasis.

By | August 1, 2012

LIGHTING UP LYMPH: Researchers discovered proteins that direct the growth of lymph vessels (green) in the developing zebrafishYoung-Ryun Cha and Brant M. Weinstein, NICHD




The paper

Y.R. Cha et al., “Chemokine signaling directs trunk lymphatic network formation along the preexisting blood vasculature,” Dev Cell, 22:824-36, 2012.



The finding

The lymphatic system, a constellation of vessels, capillaries, and nodes throughout the body, has always been difficult to study. Brant Weinstein, of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and colleagues discovered chemokine markers that guide lymphatic vessel growth during development. It’s a “major contribution to our understanding of the development of the lymphatic vasculature,” says Marc Achen of Peter MacCallum Cancer Centre in Australia, who was not involved in the study.



The technique

Weinstein’s group used transgenic embryonic zebrafish to track the formation of fluorescently labeled lymphatic vessels. The researchers mounted fish embryos in methyl cellulose, submerged them in flowing water, and imaged them with time-lapse confocal or two-photon microscopy.



The vessel tracks

The group looked at gene expression patterns for factors that might act as guidance cues. They tested the tissues surrounding the developing lymphatic network as the vessels migrated to new locations or sprouted new branches. One set of chemokine genes was expressed just before vessels arrived, then turned off. When the group knocked down the genes for those chemokines and their receptors, “we got lymphatic formation defects,” said Weinstein, whereas overexpression caused lymph vessels to form where none normally would.



The application

Researchers recently discovered that tumors stimulate the growth of new lymphatic vessels, which could be a major highway for the metastatic spread of cancer cells. As a result, there’s a great deal of interest in what signals lymph vessels to form, and these chemokines may be part of it, says Weinstein.



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