Lymphatic Metastasis of Breast Cancer Cells: Development of In Vivo Video Microscopy to Study Mechanisms of Lymphatic Spread

摘要

Metastasis via the lymphatic system is considered a major factor in mortality from breast cancer. At present there are no models for direct measurement of tumor cell spread by lymphatics. This is needed for understanding basic biology of lymphatic involvement developing treatments and assessing their effectiveness. Purpose: To develop and assess IVVM for imaging the morphology and fluid dynamics of lymphatic vessels in mouse models during tumor development. Scope: Assessment of the concept that in vivo video microscopy (IVVM) can be used for studying experimental cancer spread via the lymphatic system. Methods: Primary tumors were formed by intradermal injection of cancer cells (ventral midline between inguinal lymph nodes). IVVM was used to examine lymphatics on one side (skinflap under anesthesia, 1-25 days post injection); conventional histology used to examine other side. Results: Tumor formation was accompanied by a well developed lymphatic network adjacent to the tumor and enlarged lymphatic vessels with valves in tissues between the tumor and lymph nodes as seen by histology and lVVM. By IVVM, lymphatic endothelium and cells carried by lymph flow could be clearly seen. Conclusion: IVVM is a powerful tool for studying cancer cells as they interact with the lymphatic system.