4.8 Article

Lymph node metastases can invade local blood vessels, exit the node, and colonize distant organs in mice

期刊

SCIENCE
卷 359, 期 6382, 页码 1403-1407

出版社

AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aal3622

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资金

  1. NIH [DP2OD008780, R01CA214913, R01HL128168, T32 DK007191, P01CA080124, UL1 TR001102]
  2. National Cancer Institute (NCI) Federal Share/MGH Proton Beam Income [C06CA059267]
  3. MGH Executive Committee on Research Interim Support Funding
  4. Susan G. Komen Foundation Fellowship [PDF14301739]
  5. United Negro College Fund-Merck Science Initiative Postdoctoral Fellowship
  6. Burroughs Wellcome Postdoctoral Enrichment Program Award
  7. NIH NCI [F32CA183465]
  8. Korean Ministry of Education, Science, and Technology [NRF-2012R1A1A2040866]
  9. Samsung Biomedical Research Institute [GL1B22912]
  10. Harvard University
  11. M. Vangel and Harvard Catalyst
  12. NATIONAL CANCER INSTITUTE [F32CA183465, C06CA059267, P01CA080124, R01CA214913] Funding Source: NIH RePORTER
  13. NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES [UL1TR001102] Funding Source: NIH RePORTER
  14. NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL128168] Funding Source: NIH RePORTER
  15. NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [T32DK007191] Funding Source: NIH RePORTER
  16. OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH [DP2OD008780] Funding Source: NIH RePORTER

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Lymph node metastases in cancer patients are associated with tumor aggressiveness, poorer prognoses, and the recommendation for systemic therapy. Whether cancer cells in lymph nodes can seed distant metastases has been a subject of considerable debate. We studied mice implanted with cancer cells (mammary carcinoma, squamous cell carcinoma, or melanoma) expressing the photoconvertible protein Dendra2. This technology allowed us to selectively photoconvert metastatic cells in the lymph node and trace their fate. We found that a fraction of these cells invaded lymph node blood vessels, entered the blood circulation, and colonized the lung. Thus, in mouse models, lymph node metastases can be a source of cancer cells for distant metastases. Whether this mode of dissemination occurs in cancer patients remains to be determined.

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