In this issue of Lymphatic Research and Biology, we are pleased to include several articles focusing on lymphatic vessels and cancer. In the past decade, this field has been growing steadily but slowly, and there is still a lot to be learned about the mechanisms of lymphatic metastasis and how the lymphatic system contributes to malignant disease. Numerous studies in mouse models have shown that tumor lymphangiogenesis facilitates metastasis and two inhibitors of lymphangiogenesis, blocking antibodies to VEGFR-3 and VEGF-C, have entered clinical trials in the past year. The old view that tumor cells enter lymphatic vessels passively has been changed by the evidence that lymphatic endothelial cells attract tumor cells into the vessels by chemokines. Recent studies that showed that lymphatic endothelium can have a direct role in immunosuppression suggest that lymphatic vasculature may play a role in cancer also by modulating the immune response. It remains a particular challenge to extrapolate studies from mouse models to humans.
The authors in this special section provide insight into the lymphatic drainage in human melanoma, report on an unusual pattern of lymph node metastases in human melanoma, and investigate function of intratumoral lymphatics in human colon and pancreatic cancer. The authors discuss the differences in lymph flow in mouse and human and employ an original method for visualization of tumor lymphatics and interstitial space to assess the functionality of intratumoral lymphatic vessels. A comprehensive review on the role of lipid mediator sphingosine-1–phosphate in cancer and tumor lymphangiogenesis is also presented. This potent sphingolipid metabolite regulates a number of biological processes critical for cancer, and has been recently found to play a role also in tumor lymphangiogenesis and metastasis.
We are grateful to the contributors of this series of articles and look forward to further exciting discoveries on the topic of cancer lymphatics.
