Photodynamic ablation of lymphatic vessels and intralymphatic cancer cells prevents metastasis

Sci Transl Med. 2011 Feb 9;3(69):69ra11. doi: 10.1126/scitranslmed.3001699.

Abstract

The dissemination of tumor cells to sites far from the primary tumor (metastasis) is the principal cause of death in cancer patients. Tumor-associated lymphatic vessels are a key conduit for metastatic tumor cells, which typically first colonize the lymph nodes. Although the primary tumor and affected lymph nodes can be removed during surgery, tumor cells inside lymphatic vessels are left behind. Here, we show that in-transit tumor cells inside lymphatic vessels in mice bearing mouse melanomas or human lung tumors give rise to metastases. Using photodynamic therapy with the benzoporphyrin derivative verteporfin, we selectively destroyed lymphatic vessels in mice and pigs. Destruction of tumor-associated lymphatic vessels also eradicated intralymphatic tumor cells and prevented metastasis of mouse melanoma cells and subsequent relapse. Photodynamic therapy, when combined with anti-lymphangiogenic therapy, prevented further tumor invasion of lymphatic vessels. These findings highlight the potential of targeting in-transit tumor cells in patients.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Humans
  • Lymphatic Metastasis / prevention & control*
  • Lymphatic Vessels / drug effects*
  • Melanoma / drug therapy
  • Mice
  • Neoplasms / drug therapy*
  • Photochemotherapy / methods*
  • Photosensitizing Agents / therapeutic use
  • Porphyrins / therapeutic use
  • Swine
  • Verteporfin

Substances

  • Photosensitizing Agents
  • Porphyrins
  • Verteporfin