Cancer cells can metastasize by escaping a tumor through either blood or lymphatic vessels. Jain's group questioned whether cancerous cells escape through lymphatic vessels within the tumor itself. In various transplanted and spontaneous tumors in mice, and in human tumors, markers of lymphatic vessels were found within the tumors, but functional analysis revealed that these vessels were not draining fluid.
Jain suggests that lymphatic vessels in tumors may collapse from the high pressure exerted by the rapidly proliferating cancer cells. The findings also act as a warning against the use of markers alone to identify functioning lymphatic vessels in tumors. “A combination of markers as well as functional studies will be necessary,” Jain says.
Although lymphatic vessels in the tumor were not functional, those in the margin of the mouse tumors were either normal in appearance or, in tumors overexpressing VEGF-C, larger in diameter than normal vessels. With increased size came increased lymphatic metastasis, suggesting that marginal lymphatics are sufficient for metastasis. “The larger size of these vessels increases the opportunity for cancer cells to escape,” says Jain. Thus, radiation therapy should be directed at tumor margins in addition to their centers, and VEGF-C may provide a good target for drug treatments. ▪