Unexpected contribution of lymphatic vessels to promotion of distant metastatic tumor spread.

Ma, Qiaoli; Dieterich, Lothar C; Ikenberg, Kristian; Bachmann, Samia B; Mangana, Johanna; Proulx, Steven T.; Amann, Valerie C; Levesque, Mitchell P; Dummer, Reinhard; Baluk, Peter; McDonald, Donald M; Detmar, Michael (2018). Unexpected contribution of lymphatic vessels to promotion of distant metastatic tumor spread. Science Advances, 4(8), eaat4758. American Association for the Advancement of Science 10.1126/sciadv.aat4758

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Tumor lymphangiogenesis is accompanied by a higher incidence of sentinel lymph node metastasis and shorter overall survival in several types of cancer. We asked whether tumor lymphangiogenesis might also occur in distant organs with established metastases and whether it might promote further metastatic spread of those metastases to other organs. Using mouse metastasis models, we found that lymphangiogenesis occurred in distant lung metastases and that some metastatic tumor cells were located in lymphatic vessels and draining lymph nodes. In metastasis-bearing lungs of melanoma patients, a higher lymphatic density within and around metastases and lymphatic invasion correlated with poor outcome. Using a transgenic mouse model with inducible expression of vascular endothelial growth factor C (VEGF-C) in the lung, we found greater growth of lung metastases, with more abundant dissemination to other organs. Our findings reveal unexpected contributions of lymphatics in distant organs to the promotion of growth of metastases and their further spread to other organs, with potential clinical implications for adjuvant therapies in patients with metastatic cancer.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute

UniBE Contributor:

Proulx, Steven Thomas

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

2375-2548

Publisher:

American Association for the Advancement of Science

Language:

English

Submitter:

Ursula Zingg-Zünd

Date Deposited:

21 Nov 2019 10:18

Last Modified:

28 Nov 2020 02:30

Publisher DOI:

10.1126/sciadv.aat4758

PubMed ID:

30101193

BORIS DOI:

10.7892/boris.135344

URI:

https://boris.unibe.ch/id/eprint/135344

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