title: Photodynamic ablation of lymphatic vessels and intralymphatic cancer cells prevents metastasis.
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.
authors.affiliation: Molecular/Cancer Biology Laboratory, Faculty of Medicine Research Programs, Haartman Institute, Institute for Molecular Medicine Finland and Helsinki University Central Hospital, Biomedicum Helsinki, POB 63 (Haartmaninkatu 8), University of Helsinki, 00014 Helsinki, Finland. tuomas.tammela@helsinki.fi
authors.forename: Tuomas
authors.initials: T
authors.lastname: Tammela
authors.forename: Anne
authors.initials: A
authors.lastname: Saaristo
authors.forename: Tanja
authors.initials: T
authors.lastname: Holopainen
authors.forename: Seppo
authors.initials: S
authors.lastname: Ylä-Herttuala
authors.forename: Leif C
authors.initials: LC
authors.lastname: Andersson
authors.forename: Susanna
authors.initials: S
authors.lastname: Virolainen
authors.forename: Ilkka
authors.initials: I
authors.lastname: Immonen
authors.forename: Kari
authors.initials: K
authors.lastname: Alitalo
mesh_terms: D000818:Animals; D006801:Humans; D008207:Lymphatic Metastasis / Q000517:prevention & control*; D042601:Lymphatic Vessels / Q000187:drug effects*; D008545:Melanoma / Q000188:drug therapy; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy*; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use; D011166:Porphyrins / Q000627:therapeutic use; D013552:Swine; D000077362:Verteporfin
chemical_list: D017319:Photosensitizing Agents; D011166:Porphyrins; D000077362:Verteporfin