Nature: The lymphatic system protects tumor cells from iron death and promotes cancer cell metastasis.

Cancer cells, including melanoma cells, are usually partially transferred through the lymphatic system and then through the blood system.
, the cause is not yet clear.
August 19, 2020, the team of Sean J. Morrison of the University of Texas Southwestern Medical Center published a research paper on Nature online entitled "Lymph protects metastasize melanoma cells from ferroptosis", which showed that melanoma cells in lymphoma experienced less oxidative stress and more metastasis than melanoma cells in the blood.
DOI: Cells transferred through the blood, not through lymphatic metastasis, no longer rely on the iron death inhibitor GPX4.
intravenous but non-lymphatic injections, pre-treated cells with chemical iron death inhibitors form more metastasis than unprocessed cells.
the study observed a variety of differences between lymphatic fluid and plasma that could lead to reduced oxidative stress and reduced lymphatic iron death, including elevated glutathione and lyphosphonate levels, and decreased free iron in the lymph.
acid protects melanoma cells from iron death in an Acsl3-dependent manner and increases their ability to form metastasis tumors.
melanoma cells from the lymph nodes are more resistant to iron death and form more metastatic lesions than melanoma cells from supulocytic tumors.
, exposure to the lymphatic environment protects melanoma cells from iron death and increases their ability to survive subsequent blood transfers.
, Barbara M. Grüner and others published a review article online in Nature entitled "Cancer cells stock up in lymph vessels to survive" and systematically counted the results of the study.
melanoma and endocrine cancer usually form metastasis in the lymph nodes before they form distant metastasis.
genetic studies of cancers in humans and mice, including melanoma, have shown that local lymph node metastasis sometimes causes distant metastasis.
, cancer cells in the lymph nodes can migrate to blood vessels and then through blood.
, however, some distant metastasis is caused by different clones from the sampled lymph nodes.
these cases, it is not clear whether distant metastatic cells migrate directly from primary tumors into the bloodstream or through the lymphatic system before entering the bloodstream.
in patients with melanoma, local lymph node metastasis is one of the most important predictive indicators of distant metastasis and death.
Complete lymph node cleaning does not improve survival, however, this does not necessarily mean that distant metastasis is not related to the lymphatic system, as melanoma cells from the lymph nodes may often enter the bloodstream and spread before local metastasis is detected.
evidence that the lymphatic system promotes the migration and survival of cancer cells.
cancer cells form more tumors after injection into the lymph nodes (intravenous injections) than after intravenous injections.
C (VEGF-C) and various coercion factors promote the migration of cancer cells to the lymphatic tube.
metabolic fatty acids promote the survival of cancer cells in the lymphatic system and the formation of metastatic tumors.
, however, circulating cancer cells are mainly indicated in the blood, and little information is available about these cells compared to cancer cells in the lymphatic tubes.
although some cancer cells migrate through the lymphatic tubes before they enter the bloodstream and form distant metastasis, it is not clear whether exposure to lymphatic fluid affects the subsequent survival of these cells in the blood.
blood transfer is an inefficient process in which few cancer cells survive.
that limits survival is oxidative stress.
, however, it is not clear how oxidative stress kills metastasis cells.
lipid oxidation can cause iron death - a pattern of cell death in which polyunsaturated fatty acids in phospholipids are oxidized by redoxed active iron.
although cancer cells can die of iron in the body, most iron death studies are conducted in cultures, which limits our understanding of how iron death affects cancer growth or progression in the body.
study showed that melanoma cells in the lymphatic system experience less oxidative stress and form more metastasis than melanoma cells in the blood.
cells that are transferred through the blood, rather than through the lymphatics, are no longer dependent on the iron death inhibitor GPX4.
intravenous but non-lymphatic injections, pre-treated cells with chemical iron death inhibitors form more metastasis than unprocessed cells.
the study observed a variety of differences between lymphatic fluid and plasma that could lead to reduced oxidative stress and reduced lymphatic iron death, including elevated glutathione and lyphosphonate levels, and decreased free iron in the lymph.
acid protects melanoma cells from iron death in an Acsl3-dependent manner and increases their ability to form metastasis tumors.
melanoma cells from the lymph nodes are more resistant to iron death and form more metastatic lesions than melanoma cells from supulocytic tumors.
, exposure to the lymphatic environment protects melanoma cells from iron death and increases their ability to survive subsequent blood transfers.
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