Lysyl hydroxylase 2 induces a collagen cross-link switch in tumor stroma

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dc.citation.firstpage1147
dc.citation.issueNumber3
dc.citation.journalTitleThe Journal of Clinical Investigation
dc.citation.lastpage1162
dc.citation.volumeNumber125
dc.contributor.authorChen, Yulong
dc.contributor.authorTerajima, Masahiko
dc.contributor.authorYang, Yanan
dc.contributor.authorSun, Li
dc.contributor.authorAhn, Young-Ho
dc.contributor.authorPankova, Daniela
dc.contributor.authorPuperi, Daniel S.
dc.contributor.authorWatanabe, Takeshi
dc.contributor.authorKim, Min P.
dc.contributor.authorBlackmon, Shanda H.
dc.contributor.authorRodriguez, Jaime
dc.contributor.authorLiu, Hui
dc.contributor.authorBehrens, Carmen
dc.contributor.authorWistuba, Ignacio I.
dc.contributor.authorMinelli, Rosalba
dc.contributor.authorScott, Ken
dc.date.accessioned2016-02-05T18:38:33Z
dc.date.available2016-02-05T18:38:33Z
dc.date.issued2015
dc.description.abstractEpithelial tumor metastasis is preceded by an accumulation of collagen cross-links that heighten stromal stiffness and stimulate the invasive properties of tumor cells. However, the biochemical nature of collagen cross-links in cancer is still unclear. Here, we postulated that epithelial tumorigenesis is accompanied by changes in the biochemical type of collagen cross-links. Utilizing resected human lung cancer tissues and a p21CIP1/WAF1-deficient, K-rasG12D-expressing murine metastatic lung cancer model, we showed that, relative to normal lung tissues, tumor stroma contains higher levels of hydroxylysine aldehyde–derived collagen cross-links (HLCCs) and lower levels of lysine aldehyde–derived cross-links (LCCs), which are the predominant types of collagen cross-links in skeletal tissues and soft tissues, respectively. Gain- and loss-of-function studies in tumor cells showed that lysyl hydroxylase 2 (LH2), which hydroxylates telopeptidyl lysine residues on collagen, shifted the tumor stroma toward a high-HLCC, low-LCC state, increased tumor stiffness, and enhanced tumor cell invasion and metastasis. Together, our data indicate that LH2 enhances the metastatic properties of tumor cells and functions as a regulatory switch that controls the relative abundance of biochemically distinct types of collagen cross-links in the tumor stroma.
dc.identifier.citationChen, Yulong, Terajima, Masahiko, Yang, Yanan, et al.. "Lysyl hydroxylase 2 induces a collagen cross-link switch in tumor stroma." <i>The Journal of Clinical Investigation,</i> 125, no. 3 (2015) American Society for Clinical Investigation: 1147-1162. http://dx.doi.org/10.1172/JCI74725.
dc.identifier.doihttp://dx.doi.org/10.1172/JCI74725
dc.identifier.urihttps://hdl.handle.net/1911/88401
dc.language.isoeng
dc.publisherAmerican Society for Clinical Investigation
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
dc.titleLysyl hydroxylase 2 induces a collagen cross-link switch in tumor stroma
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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