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Active remodeling of capillary endothelium via cancer cell-derived MMP9 promotes metastatic brain colonization

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Active remodeling of capillary endothelium via cancer cell-derived MMP9 promotes metastatic brain colonization. / Karreman, Matthia A; Bauer, Alexander T; Solecki, Gergely; Berghoff, Anna S; Mayer, Chanté D; Frey, Katharina; Hebach, Nils; Feinauer, Manuel J; Schieber, Nicole L; Tehranian, Cedric; Mercier, Luc; Singhal, Mahak; Venkataramani, Varun; Schubert, Marc C; Hinze, Daniel; Hölzel, Michael; Helfrich, Iris; Schadendorf, Dirk; Schneider, Stefan W; Westphal, Dana; Augustin, Hellmut G; Goetz, Jacky G; Schwab, Yannick; Wick, Wolfgang; Winkler, Frank.

In: CANCER RES, Vol. 83, No. 8, 14.04.2023, p. 1299-1314.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Karreman, MA, Bauer, AT, Solecki, G, Berghoff, AS, Mayer, CD, Frey, K, Hebach, N, Feinauer, MJ, Schieber, NL, Tehranian, C, Mercier, L, Singhal, M, Venkataramani, V, Schubert, MC, Hinze, D, Hölzel, M, Helfrich, I, Schadendorf, D, Schneider, SW, Westphal, D, Augustin, HG, Goetz, JG, Schwab, Y, Wick, W & Winkler, F 2023, 'Active remodeling of capillary endothelium via cancer cell-derived MMP9 promotes metastatic brain colonization', CANCER RES, vol. 83, no. 8, pp. 1299-1314. https://doi.org/10.1158/0008-5472.CAN-22-3964

APA

Karreman, M. A., Bauer, A. T., Solecki, G., Berghoff, A. S., Mayer, C. D., Frey, K., Hebach, N., Feinauer, M. J., Schieber, N. L., Tehranian, C., Mercier, L., Singhal, M., Venkataramani, V., Schubert, M. C., Hinze, D., Hölzel, M., Helfrich, I., Schadendorf, D., Schneider, S. W., ... Winkler, F. (2023). Active remodeling of capillary endothelium via cancer cell-derived MMP9 promotes metastatic brain colonization. CANCER RES, 83(8), 1299-1314. https://doi.org/10.1158/0008-5472.CAN-22-3964

Vancouver

Karreman MA, Bauer AT, Solecki G, Berghoff AS, Mayer CD, Frey K et al. Active remodeling of capillary endothelium via cancer cell-derived MMP9 promotes metastatic brain colonization. CANCER RES. 2023 Apr 14;83(8):1299-1314. https://doi.org/10.1158/0008-5472.CAN-22-3964

Bibtex

@article{d8fd013020de4c6097ff160dbfc2a6d4,
title = "Active remodeling of capillary endothelium via cancer cell-derived MMP9 promotes metastatic brain colonization",
abstract = "UNLABELLED: 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 endpoint 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 (EC) 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 cross-talk between the two cell types. This extends our understanding of how host cells can contribute to brain metastasis formation and how to prevent it.SIGNIFICANCE: Tracking single extravasating cancer cells using multimodal correlative microscopy uncovers a brain seeding mechanism involving endothelial remodeling driven by cancer cell-derived MMP9, which might enable the development of approaches to prevent brain metastasis. See related commentary by McCarty, p. 1167.",
author = "Karreman, {Matthia A} and Bauer, {Alexander T} and Gergely Solecki and Berghoff, {Anna S} and Mayer, {Chant{\'e} D} and Katharina Frey and Nils Hebach and Feinauer, {Manuel J} and Schieber, {Nicole L} and Cedric Tehranian and Luc Mercier and Mahak Singhal and Varun Venkataramani and Schubert, {Marc C} and Daniel Hinze and Michael H{\"o}lzel and Iris Helfrich and Dirk Schadendorf and Schneider, {Stefan W} and Dana Westphal and Augustin, {Hellmut G} and Goetz, {Jacky G} and Yannick Schwab and Wolfgang Wick and Frank Winkler",
year = "2023",
month = apr,
day = "14",
doi = "10.1158/0008-5472.CAN-22-3964",
language = "English",
volume = "83",
pages = "1299--1314",
journal = "CANCER RES",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "8",

}

RIS

TY - JOUR

T1 - Active remodeling of capillary endothelium via cancer cell-derived MMP9 promotes metastatic brain colonization

AU - Karreman, Matthia A

AU - Bauer, Alexander T

AU - Solecki, Gergely

AU - Berghoff, Anna S

AU - Mayer, Chanté D

AU - Frey, Katharina

AU - Hebach, Nils

AU - Feinauer, Manuel J

AU - Schieber, Nicole L

AU - Tehranian, Cedric

AU - Mercier, Luc

AU - Singhal, Mahak

AU - Venkataramani, Varun

AU - Schubert, Marc C

AU - Hinze, Daniel

AU - Hölzel, Michael

AU - Helfrich, Iris

AU - Schadendorf, Dirk

AU - Schneider, Stefan W

AU - Westphal, Dana

AU - Augustin, Hellmut G

AU - Goetz, Jacky G

AU - Schwab, Yannick

AU - Wick, Wolfgang

AU - Winkler, Frank

PY - 2023/4/14

Y1 - 2023/4/14

N2 - UNLABELLED: 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 endpoint 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 (EC) 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 cross-talk between the two cell types. This extends our understanding of how host cells can contribute to brain metastasis formation and how to prevent it.SIGNIFICANCE: Tracking single extravasating cancer cells using multimodal correlative microscopy uncovers a brain seeding mechanism involving endothelial remodeling driven by cancer cell-derived MMP9, which might enable the development of approaches to prevent brain metastasis. See related commentary by McCarty, p. 1167.

AB - UNLABELLED: 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 endpoint 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 (EC) 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 cross-talk between the two cell types. This extends our understanding of how host cells can contribute to brain metastasis formation and how to prevent it.SIGNIFICANCE: Tracking single extravasating cancer cells using multimodal correlative microscopy uncovers a brain seeding mechanism involving endothelial remodeling driven by cancer cell-derived MMP9, which might enable the development of approaches to prevent brain metastasis. See related commentary by McCarty, p. 1167.

U2 - 10.1158/0008-5472.CAN-22-3964

DO - 10.1158/0008-5472.CAN-22-3964

M3 - SCORING: Journal article

C2 - 36652557

VL - 83

SP - 1299

EP - 1314

JO - CANCER RES

JF - CANCER RES

SN - 0008-5472

IS - 8

ER -