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Tumor Biology

, Volume 33, Issue 6, pp 2135–2141 | Cite as

Effects of hyaluronic acid and CD44 interaction on the proliferation and invasiveness of malignant pleural mesothelioma

  • Takeshi Hanagiri
  • Shinji Shinohara
  • Masaru Takenaka
  • Yoshiki Shigematsu
  • Manabu Yasuda
  • Hidehiko Shimokawa
  • Yoshika Nagata
  • Makoto Nakagawa
  • Hidetaka Uramoto
  • Tomoko So
  • Fumihiro Tanaka
Research Article

Abstract

Hyaluronic acid (HA) has been proposed as a biochemical marker of malignant pleural mesothelioma (MPM). The present study focused on the implications of HA and CD44 interaction in the proliferation and invasiveness of MPM. The proliferation and invasive activity was evaluated in two human mesothelioma cell lines, ACC-MESO-1 and K921MSO, by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and the transwell chamber model. The knockdown of CD44 gene expression was accomplished by transfection of the cells with small interfering RNA. Flow cytometry revealed that both the ACC-MESO-1 and K921MSO cell lines highly expressed CD44. Treatment with HA enhanced the proliferation in both mesothelioma cell lines in comparison to cells without HA treatment. The treatment with HA (25 μg/ml) also significantly upregulated the invasion of both types of cells. The silencing of CD44 significantly abrogated the effect of HA treatment on the proliferation of ACC-MESO-1 cells and significantly suppressed the proliferation of K921MSO cells. HA–CD44 binding is important for the migration and proliferation of mesothelioma cells. Therefore, the HA–CD44 interaction is a potentially useful therapeutic target in MPM.

Keywords

Malignant pleural mesothelioma Hyaluronic acid CD44 Proliferation 

Notes

Acknowledgments

This study was supported in part by a UOEH Research Grant for the Promotion of Occupational Health and a Grant-in-Aid for scientific research from the Ministry of Education, Culture, Sports, Science and Technology, Japan. We thank Yukari Furutani, Misako Fukumoto, and Yukiko Koyanagi for their expert technical help.

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2012

Authors and Affiliations

  • Takeshi Hanagiri
    • 1
  • Shinji Shinohara
    • 1
  • Masaru Takenaka
    • 1
  • Yoshiki Shigematsu
    • 1
  • Manabu Yasuda
    • 1
  • Hidehiko Shimokawa
    • 1
  • Yoshika Nagata
    • 1
  • Makoto Nakagawa
    • 1
  • Hidetaka Uramoto
    • 1
  • Tomoko So
    • 1
  • Fumihiro Tanaka
    • 1
  1. 1.Second Department of Surgery, School of MedicineUniversity of Occupational and Environmental HealthKitakyushuJapan

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