Journal Article

DKFZ-2023-00116

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Active remodeling of capillary endothelium via cancer cell-derived MMP9 promotes metastatic brain colonization.

Karreman, M. A. (First author)DKFZ* ; Bauer, A. T. ; Solecki, G. M.DKFZ* ; Berghoff, A. S.DKFZ* ; Mayer, C. D.DKFZ* ; Frey, K.DKFZ* ; Hebach, N.DKFZ* ; Feinauer, M.DKFZ* ; Schieber, N. L. ; Tehranian, C.DKFZ* ; Mercier, L. ; Singhal, M.DKFZ* ; Venkataramani, V.DKFZ* ; Schubert, M. C. ; Hinze, D. ; Hölzel, M. ; Helfrich, I.DKFZ* ; Schadendorf, D.DKFZ* ; Schneider, S. W. ; Westphal, D. ; Augustin, H.DKFZ* ; Goetz, J. G. ; Schwab, Y. ; Wick, W.DKFZ* ; Winkler, F. (Last author)DKFZ*

2023
AACR Philadelphia, Pa.

This record in other databases:  

Please use a persistent id in citations: doi:10.1158/0008-5472.CAN-22-3964

Abstract: Crossing the blood-brain barrier is a crucial, rate-limiting step of brain metastasis. Understanding of the mechanisms of cancer cell extravasation from brain microcapillaries is limited as the underlying cellular and molecular processes cannot be adequately investigated using in vitro models and end-point in vivo experiments. Using ultrastructural and functional imaging, we demonstrate that dynamic changes of activated brain microcapillaries promote the mandatory first steps of brain colonization. Successful extravasation of arrested cancer cells occurred when adjacent capillary endothelial cells (ECs) entered into a distinct remodeling process. After extravasation, capillary loops were formed, which was characteristic of aggressive metastatic growth. Upon cancer cell arrest in brain microcapillaries, matrix-metalloprotease 9 (MMP9) was expressed. Inhibition of MMP2/9 and genetic perturbation of MMP9 in cancer cells, but not the host, reduced EC projections, extravasation, and brain metastasis outgrowth. These findings establish an active role of ECs in the process of cancer cell extravasation, facilitated by crosstalk between the two cell types. This extends our understanding of how host cells can contribute to brain metastasis formation and how to prevent it.

Note: DKFZ-ZMBH Alliance / #EA:B320#LA:B320# / 2023 Apr 14;83(8):1299-1314

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Contributing Institute(s):

1. KKE Neuroonkologie (B320)
2. DKTK HD zentral (HD01)
3. A190 Vaskuläre Onkologie und Metastasierung (A190)
4. DKTK ED ES zentral (ED01)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2023

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 10 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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