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

The Journal of clinical investigation (2015-02-11)
Yulong Chen, Masahiko Terajima, Yanan Yang, Li Sun, Young-Ho Ahn, Daniela Pankova, Daniel S Puperi, Takeshi Watanabe, Min P Kim, Shanda H Blackmon, Jaime Rodriguez, Hui Liu, Carmen Behrens, Ignacio I Wistuba, Rosalba Minelli, Kenneth L Scott, Johannah Sanchez-Adams, Farshid Guilak, Debananda Pati, Nishan Thilaganathan, Alan R Burns, Chad J Creighton, Elisabeth D Martinez, Tomasz Zal, K Jane Grande-Allen, Mitsuo Yamauchi, Jonathan M Kurie
RESUMEN

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 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.

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Ethanol, anhydrous, denatured
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Ethanol, BioUltra, for molecular biology, ≥99.8%, (absolute alcohol, without additive, A15 o1)
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Acetone, ACS reagent, ≥99.5%
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Ethanol, for residue analysis
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Ethanol, standard for GC
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Ethanol, purum, secunda spirit, denaturated with 2% 2-butanone and 0.5% 4-methyl-2-pentanone, S15, ~96% (based on denaturant-free substance)
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Ethanol, tested according to Ph. Eur.
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Formaldehyde solution, ACS reagent, 37 wt. % in H2O, contains 10-15% Methanol as stabilizer (to prevent polymerization)
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Acetone, HPLC Plus, for HPLC, GC, and residue analysis, ≥99.9%
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Sodium dodecyl sulfate, BioReagent, suitable for electrophoresis, for molecular biology, ≥98.5% (GC)
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Formaldehyde solution, for molecular biology, 36.5-38% in H2O
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Sodium dodecyl sulfate, ACS reagent, ≥99.0%
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Thiazolyl Blue Tetrazolium Bromide, 98%
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Acetone, suitable for HPLC, ≥99.9%
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Ethylenediaminetetraacetic acid, BioUltra, anhydrous, ≥99% (titration)
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Thiazolyl Blue Tetrazolium Bromide, powder, BioReagent, suitable for cell culture, suitable for insect cell culture, ≥97.5% (HPLC)
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Ethylenediaminetetraacetic acid, ACS reagent, 99.4-100.6%, powder
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Sodium dodecyl sulfate, ReagentPlus®, ≥98.5% (GC)
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Sodium dodecyl sulfate, BioUltra, for molecular biology, ≥99.0% (GC)
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Sodium dodecyl sulfate, ≥99.0% (GC), dust-free pellets
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Ethylenediaminetetraacetic acid, anhydrous, crystalline, BioReagent, suitable for cell culture
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Formaldehyde solution, contains 10-15% methanol as stabilizer, 37 wt. % in H2O
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Ethyl alcohol, Pure, 200 proof, meets USP testing specifications
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Sodium dodecyl sulfate solution, BioUltra, for molecular biology, 20% in H2O
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Formaldehyde solution, for molecular biology, BioReagent, ≥36.0% in H2O (T)
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