Editor's Note: LOX-Mediated Collagen Cross-linking Is Responsible for Fibrosis-Enhanced Metastasis
In: Cancer research, Jg. 79 (2019-10-03), Heft 19
Online
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Zugriff:
Tumor metastasis is a highly complex, dynamic and inefficient process involving multiple steps, yet accounts for over 90% of cancer patient deaths. Although it has long been known that fibrotic signals enhance tumor progression and metastasis, the underlying molecular mechanisms are still unclear. Identifying events involved in creating environments that promote metastatic colonization and growth is critical for the development of effective cancer therapies. Here, we demonstrate a critical role for lysyl oxidase (LOX) in establishing a milieu within fibrosing tissues that is favorable to growth of metastastic tumor cells. We show that LOX-dependent collagen crosslinking is involved in creating a growth-permissive fibrotic microenvironment capable of supporting metastatic growth by enhancing tumor cell persistence and survival. We show that therapeutic targeting of LOX abrogates not only the extent to which fibrosis manifests, but also prevents fibrosis-enhanced metastatic colonization. Finally, we show that the LOX-mediated collagen cross-linking directly increases tumor cell proliferation, enhancing metastatic colonization and growth manifesting in vivo as increased metastasis. This is the first time that crosslinking of collagen I has been shown to enhance metastatic growth. These findings provide an important link between extracellular matrix homeostasis, fibrosis and cancer with important clinical implications for both the treatment of fibrotic disease and cancer.
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Editor's Note: LOX-Mediated Collagen Cross-linking Is Responsible for Fibrosis-Enhanced Metastasis
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Autor/in / Beteiligte Person: | Barker, Holly E. ; Lang, Georgina ; Bird, Demelza ; Erler, Janine T. ; Melisa W.-Y. Ho ; Baker, Ann-Marie ; Cox, Thomas R. |
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Zeitschrift: | Cancer research, Jg. 79 (2019-10-03), Heft 19 |
Veröffentlichung: | 2019 |
Medientyp: | unknown |
ISSN: | 1538-7445 (print) |
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