Laminin-1-derived scrambled peptide AG73T disaggregates laminin-1-induced ovarian cancer cell spheroids and improves the efficacy of cisplatin

  • Authors:
    • Yoshio Yoshida
    • Tetsuji Kurokawa
    • Yukiko Nishikawa
    • Makoto Orisa
    • Hynda K. Kleinman
    • Fumikazu Kotsuji
  • View Affiliations

  • Published online on: March 1, 2008     https://doi.org/10.3892/ijo.32.3.673
  • Pages: 673-681
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Abstract

We found previously that the laminin-1-derived synthetic peptide AG73 (LQVQLSIR) promoted ovarian cancer cell metastasis in vivo. We have now studied the role of this metastasis-promoting peptide in vitro using TAC3 ovarian cancer cells, which display anchorage-independent growth and form multicellular spheroids. Our goal is to better understand how this peptide can regulate metastasis in vivo. We found that the exogenous addition of either laminin-1 or peptide AG73 stimulated the formation and growth of the spheroids. Western blot analysis indicated that laminin-1 enhanced the expression of integrin β1, and that AG73 peptide enhanced expression of syndecan-1 and downstream effectors, including mitogen-activated protein kinase (MAPK) and extracellular signal-related kinase (ERK), and also phosphatidylinositol (PI)-3 kinase/AKT activity signaling. The soluble peptide AG73T, which is a scramble peptide of AG73, was able to disaggregate the laminin-1-induced spheroids. Furthermore, the disaggregated cells were twice as sensitive to cisplatin as the intact spheroids. The AG73T peptide in the presence of laminin-1 suppressed expression of integrin β1 and its downstream effectors, including MAPK/ERK and PI3/AKT activity signaling. The MEK inhibitor U0126 reduced TAC3 cell growth more effectively in the presence of both laminin-1 and AG73T than in the presence of laminin-1 alone. Inhibition of the PI3-K cascade with LY294002 was also more effective in the presence of laminin-1 and AG73T. The increased sensitivity to cisplatin in the presence of AG73T may be due to the greater bioavailability of the drug to the free-floating cells over the spheroids. These findings suggest a novel function of AG73T in ovarian cancer and help to define mechanisms important in ovarian cancer spheroid formation and spread.

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March 2008
Volume 32 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Yoshida Y, Kurokawa T, Nishikawa Y, Orisa M, Kleinman HK and Kotsuji F: Laminin-1-derived scrambled peptide AG73T disaggregates laminin-1-induced ovarian cancer cell spheroids and improves the efficacy of cisplatin. Int J Oncol 32: 673-681, 2008
APA
Yoshida, Y., Kurokawa, T., Nishikawa, Y., Orisa, M., Kleinman, H.K., & Kotsuji, F. (2008). Laminin-1-derived scrambled peptide AG73T disaggregates laminin-1-induced ovarian cancer cell spheroids and improves the efficacy of cisplatin. International Journal of Oncology, 32, 673-681. https://doi.org/10.3892/ijo.32.3.673
MLA
Yoshida, Y., Kurokawa, T., Nishikawa, Y., Orisa, M., Kleinman, H. K., Kotsuji, F."Laminin-1-derived scrambled peptide AG73T disaggregates laminin-1-induced ovarian cancer cell spheroids and improves the efficacy of cisplatin". International Journal of Oncology 32.3 (2008): 673-681.
Chicago
Yoshida, Y., Kurokawa, T., Nishikawa, Y., Orisa, M., Kleinman, H. K., Kotsuji, F."Laminin-1-derived scrambled peptide AG73T disaggregates laminin-1-induced ovarian cancer cell spheroids and improves the efficacy of cisplatin". International Journal of Oncology 32, no. 3 (2008): 673-681. https://doi.org/10.3892/ijo.32.3.673