Clinical & Experimental Metastasis

, Volume 24, Issue 7, pp 541–550 | Cite as

Interaction of MT1-MMP and laminin-5γ2 chain correlates with metastasis and invasiveness in human esophageal squamous cell carcinoma

  • Xiao-Ming Shen
  • Yu-Peng Wu
  • Yan-Bin Feng
  • Man-Li Luo
  • Xiao-Li Du
  • Yu Zhang
  • Yan Cai
  • Xin Xu
  • Ya-Ling Han
  • Xun Zhang
  • Qi-Min Zhan
  • Ming-Rong Wang
Research Paper

Abstract

To gain insights into metastatic mechanisms in esophageal squamous cell carcinoma (ESCC), we established sublines (MLuB1 and MLuC1) with different capacity of spontaneous lung metastasis by subcutaneous injection of a human ESCC cell line (EC 9706) into nude mices. The incidence of the mice with lung metastasis produced by MLuC1 (87%) was significantly higher than that of MLuB1 (22%). The gene expression profiles of the two sublines were compared with cDNA arrays containing 5,000 known genes, and 47 genes were differentially expressed ≥2.0 fold. Laminin-5γ2 chain (Ln-5γ2) was one of the up-regulated genes in MLuC1 cells. Proteolytically processed forms of γ2 are known to promote migration of a multitude of epithelial cells in vitro. Western-blotting analysis revealed that degraded fragments of Ln-5γ2 and active form of membrane-type matrix metalloproteinase-1 (MT1-MMP) in MLuC1 was significantly higher than those in MLuB1. Expression of MT1-MMP was observed in 60 of 75 Ln-5γ2-positive carcinoma tissues (80%). Co-expression of the two proteins was significantly associated with depth of invasion (P = 0.012). Moreover, proteolytic fragments of Ln-5γ2 and active forms of MT1-MMP were frequently found in tumor tissues, whereas in the corresponding normal esophageal tissues there were only intact forms of γ2 and MT1-MMP. siRNA-mediated silencing of MT1-MMP significantly reduced production of γ2′ and γ2x in MLuC1 cells and inhibited cell migration. The results suggest that MT1-MMP is an enzyme responsible for Ln-5γ2 cleavage in ESCC, and interaction between them may play a critical role in promoting invasion and metastasis of human ESCC.

Keywords

Esophageal squamous cell carcinoma Invasion Ln-5γ2 MT1-MMP Nude mice Spontaneous metastasis 

Abbreviations

Ln-5γ2

Laminin-5γ2

MT1-MMP

Membrane-type matrix metalloproteinase-1

ESCC

Esophageal squamous cell carcinoma

GAPDH

Glyceralde-3-phosphate dehydrogenase

CA12

Carbonic anhydrase XII

HMGA2

High mobility group AT-hook 2

CTSS

Cathepsin S

COL4A6

Collagen type IV alpha 6

COL7A1

Collage type VII alpha 1

TSPAN-1

Tetraspan 1

Supplementary material

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Copyright information

© Springer Science + Business Media B.V. 2007

Authors and Affiliations

  • Xiao-Ming Shen
    • 1
  • Yu-Peng Wu
    • 1
  • Yan-Bin Feng
    • 1
  • Man-Li Luo
    • 1
  • Xiao-Li Du
    • 1
  • Yu Zhang
    • 1
  • Yan Cai
    • 1
  • Xin Xu
    • 1
  • Ya-Ling Han
    • 1
  • Xun Zhang
    • 2
  • Qi-Min Zhan
    • 1
  • Ming-Rong Wang
    • 1
  1. 1.State Key Laboratory of Molecular Oncology, Cancer Institute (Hospital)Peking Union Medical College and Chinese Academy of Medical SciencesBeijingChina
  2. 2.Department of Pathology, Cancer Institute (Hospital)Peking Union Medical College and Chinese Academy of Medical SciencesBeijingChina

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