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Lysyl hydroxylase 2 induces a collagen cross-link switch in tumor stroma
- Title
- Lysyl hydroxylase 2 induces a collagen cross-link switch in tumor stroma
- Authors
- Chen, Yulong; Terajima, Masahiko; Yang, Yanan; Sun, Li; Ahn, Young-Ho; Pankova, Daniela; Puperi, Daniel S.; Watanabe, Takeshi; Kim, Min P.; Blackmon, Shanda H.; Rodriguez, Jaime; Liu, Hui; Behrens, Carmen; Wistuba, Ignacio I.; Minelli, Rosalba; Scott, Kenneth L.; Sanchez-Adams, Johannah; Guilak, Farshid; Pati, Debananda; Thilaganathan, Nishan; Burns, Alan R.; Creighton, Chad J.; Martinez, Elisabeth D.; Zal, Tomasz; Grande-Allen, K. Jane; Yamauchi, Mitsuo; Kurie, Jonathan M.
- Ewha Authors
- 안영호
- SCOPUS Author ID
- 안영호
- Issue Date
- 2015
- Journal Title
- JOURNAL OF CLINICAL INVESTIGATION
- ISSN
- 0021-9738
1558-8238
- Citation
- JOURNAL OF CLINICAL INVESTIGATION vol. 125, no. 3, pp. 1147 - 1162
- Publisher
- AMER SOC CLINICAL INVESTIGATION INC
- Indexed
- SCI; SCIE; SCOPUS
- Document Type
- Article
- Abstract
- Epithelial 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 p21(CIP1/WAF1)-deficient, K-ras(G12D)-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.
- DOI
- 10.1172/JCI74725
- Appears in Collections:
- 의과대학 > 의학과 > Journal papers
- Files in This Item:
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