SCCOHT tumors acquire chemoresistance and protection by interacting mesenchymal stroma/stem cells within the tumor microenvironment

  • Authors:
    • Anna Otte
    • Yuanyuan Yang
    • Juliane von der Ohe
    • Catharina Melzer
    • Peter Hillemanns
    • Friedrich Feuerhake
    • Ralf Hass
  • View Affiliations

  • Published online on: October 14, 2016     https://doi.org/10.3892/ijo.2016.3735
  • Pages: 2453-2463
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Abstract

Chemotherapeutic drug testing of SCCOHT-1 and BIN-67 tumor cells revealed synergistic growth-inhibition of >95% in vitro with a combination of foretinib and FK228. Application of this drug combination in vivo in NODscid mice-induced SCCOHT-1GFP tumors was associated with ~6-fold reduction in tumor mass within 10 days, whereby synergistic effects of the two compounds remained undetectable compared to previous results with foretinib treatment alone. Histopathologic evaluation revealed a reduced vascularization and a lower amount of proliferating cells in the treated tumors. Surprisingly, a simultaneous significant accumulation of extracellular matrix structures with positive elastin-van Gieson staining was observed following foretinib/FK228 exposure. Expression analysis of treated animal tumors exhibited various changes including increased mouse transcript levels of elastin, laminin, and fibronectin. In parallel, markers for mesenchymal stroma/stem cells (MSC) including CD73 and CD90 were detectable in all mouse tumors suggesting a possible involvement of these cells in extracellular matrix restructure. Indeed, incubation of MSC with FK228 or foretinib/FK228 demonstrated morphologic alterations and enhanced expression of laminin and fibronectin. Moreover, a co-culture of MSC with lentiviral-labeled SCCOHT-1GFP cells contributed to protection of the tumor cells against FK228-mediated cytotoxicity. Furthermore, explant cultures of SCCOHT-1GFP-induced tumors acquired an increased resistance to FK228 and a combination of foretinib/FK228 in contrast to foretinib alone. Together, these data suggested that FK228-mediated extracellular matrix protein expression by MSC contributes to increased protection and enhanced resistance of SCCOHT tumors which could represent a more general mechanism of MSC during drug-induced alterations of a tumor microenvironment.
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December-2016
Volume 49 Issue 6

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

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Spandidos Publications style
Otte A, Yang Y, von der Ohe J, Melzer C, Hillemanns P, Feuerhake F and Hass R: SCCOHT tumors acquire chemoresistance and protection by interacting mesenchymal stroma/stem cells within the tumor microenvironment. Int J Oncol 49: 2453-2463, 2016
APA
Otte, A., Yang, Y., von der Ohe, J., Melzer, C., Hillemanns, P., Feuerhake, F., & Hass, R. (2016). SCCOHT tumors acquire chemoresistance and protection by interacting mesenchymal stroma/stem cells within the tumor microenvironment. International Journal of Oncology, 49, 2453-2463. https://doi.org/10.3892/ijo.2016.3735
MLA
Otte, A., Yang, Y., von der Ohe, J., Melzer, C., Hillemanns, P., Feuerhake, F., Hass, R."SCCOHT tumors acquire chemoresistance and protection by interacting mesenchymal stroma/stem cells within the tumor microenvironment". International Journal of Oncology 49.6 (2016): 2453-2463.
Chicago
Otte, A., Yang, Y., von der Ohe, J., Melzer, C., Hillemanns, P., Feuerhake, F., Hass, R."SCCOHT tumors acquire chemoresistance and protection by interacting mesenchymal stroma/stem cells within the tumor microenvironment". International Journal of Oncology 49, no. 6 (2016): 2453-2463. https://doi.org/10.3892/ijo.2016.3735