The role of Hyaluronan-triggering epithelial to mesenchymal transition on multidrug resistance in malignant mesohtlioma cells.

2011 Fiscal Year Final Research Report

• Project/Area Number: 22700889
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Tumor biology
• Research Institution: Hyogo University of Health Sciences
• Principal Investigator: OHNO Yoshiya 兵庫医療大学, 薬学部, 助教 (40509155)
• Project Period (FY): 2010 – 2011
• Keywords: 癌 / ヒアルロン酸 / 接着分子 / 上皮間葉転換

Research Abstract

Low intermediate molecular weight hyaluronan(HA) triggered epithelial-to-mesenchymal transition(EMT) and enhanced chemoresistance in malignant mesothelioma cells. Additionally, chemosensitivy of mesothelioma cells were resulted in a slight improvement by blocking of HA-CD44 signaling. Subpopulation equipped with cancer stem cells(CSCs)-associated properties were founded in mesothelioma spheroids expressing EMT markers. CSC-like subpopulation showed up-regulation of hyaluronan synthases(HAS) and were suppressed in the presence of hyaluronan synthases inhibitor, 4-methylumbelliferone(4MU). These results suggested that hyaluronan mediated regulation of EMT-and CSCs-properties related with chemoresistance on malignant mesothelioma cells.

Research Products

• [Journal Article] Anti-tumor effect against human cancer xenografts by a fully human monoclonal antibody to a variant 8-epitope of CD44R1 expressed on cancer stem cells (2012)
  • Author(s): Masuko. K, Okazaki S., Satoh M., Tanaka G., Ikeda T., Torii R., Ueda E., Nakano T., Danbayashi M., Tsuruoka T., Ohno Y., Yagi H., Yabe N., Yoshida H., Tahara T., Kataoka S., Oshino T., Shindo T., Niwa S., Ishimoto T., Baba H., Hashimoto Y., Saya H. & Masu
  • Journal Title: PLoS One Volume: 7 Pages: e29728
  • Peer Reviewed
• [Journal Article] Oncogenicity of L-type amino-acid transporter 1(LAT1) revealed by targeted gene disruption in chicken DT40 cells : LAT1 is a promising molecular target for human cancer therapy (2011)
  • Author(s): Ohkawa M., Ohno, Y., Masuko K., Takeuchi A., Suda K., Kubo A., Kawahara R., Okazaki S., Tanaka T., Saya H., Seki M., Enomoto T., Yagi H., Hashimoto Y. & Masuko T.
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 406 Pages: 649-655
  • Peer Reviewed
• [Journal Article] Towards therapeutic antibodies to membrane oncoproteins by a robust strategy using rats immunized with transfectants expressing target molecules fused to green fluorescent protein (2011)
  • Author(s): Masuko T, Ohno Y, Masuko K, Yagi H, Uejima S, Takechi M, Hashimoto Y.
  • Journal Title: Cancer Sci Volume: 102 Pages: 25-35
  • Peer Reviewed
• [Journal Article] NIH3T3 cells over-expressing CD98 heavy chain resist early G1 arrest and apoptosis induced by serum starvation
  • Author(s): Hara K., Ueda S., Ohno Y., Tanaka T., Yagi H., Okazaki S., Kawahara R., Masayuki T., Enomoto T., Hashimoto Y., Masuko K. & Masuko T
  • Journal Title: Cancer Sci Volume: (in press)
  • Peer Reviewed
• [Remarks]
  • URL: http://www2.huhs.ac.jp/～h080065y/index.html