Is lymphatic pumping safe for breast cancer patients?: The role of lymphatic flow in tumor formation and metastasis (46.19)

Abstract

Lymphedema, a common side effect of breast cancer, can only be treated effectively with techniques such as pneumatic compression, exercise, massage, and osteopathic manipulation. However, the effect of such therapies on tumors and metastases is unknown. We have developed a murine model to test the effect of abdominal lymphatic pump treatment (LPT) on cancer. F344 rats were injected intravenously or subcutaneously with MADB106 mammary carcinoma cells. Rats were then given 4 minutes of LPT under anesthesia, 4 minutes of light touch under anesthesia (sham), or no treatment (control) for 7 days. At day 8, lung tissues were analyzed for metastases, and for leukocyte number/activity. LPT on intravenously-inoculated rats reduced tumor metastases in the lungs by more than 40% compared to sham and control. This corresponded with an increase in IFN-γ, and in CCR9+CD4+, CCR9+CD8+, and CCR9+ NK cells in the lungs, suggesting that these cells were actually gut-derived. Interestingly, in the case of subcutaneous solid tumors, LPT may be detrimental, as tumor size and number of metastases were more than doubled. These data suggest that increasing lymphatic flow may mobilize gut-derived leukocytes, which can traffic to the lungs and confer protection against tumor metastases, possibly through IFN-γ. To our knowledge, this is the first time gut-derived cells have been shown to be protective in the lungs. However, these therapies may cause harm when performed in proximity to solid tumors.