July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Recruitment and activation of hepatic stellate cells by uveal melanoma cells in a xenograft mouse model
Author Affiliations & Notes
  • Léo PIQUET
    CUO-Recherche/Axe médecine régénératrice, Centre de recherche du CHU de Québec-Université Laval, Québec, Quebec, Canada
    Département d'ophtalmologie, Université Laval, Québec, Quebec, Canada
  • Peter Gerges
    CUO-Recherche/Axe médecine régénératrice, Centre de recherche du CHU de Québec-Université Laval, Québec, Quebec, Canada
  • William Pelletier
    CUO-Recherche/Axe médecine régénératrice, Centre de recherche du CHU de Québec-Université Laval, Québec, Quebec, Canada
  • Julie Bérubé
    CUO-Recherche/Axe médecine régénératrice, Centre de recherche du CHU de Québec-Université Laval, Québec, Quebec, Canada
  • Frédéric Mouriaux
    UMR 1241 NUMECAN (Nutrition, Métabolisme et Cancer), Université Rennes 1, Rennes, France
    Département d'ophtalmologie, Université Laval, Québec, Quebec, Canada
  • Arnaud de la Fouchardière
    Département de biopathologie, Centre Léon Bérard, Lyon, France
  • Solange Landreville
    CUO-Recherche/Axe médecine régénératrice, Centre de recherche du CHU de Québec-Université Laval, Québec, Quebec, Canada
    Département d'ophtalmologie, Université Laval, Québec, Quebec, Canada
  • Footnotes
    Commercial Relationships   Léo PIQUET, None; Peter Gerges, None; William Pelletier, None; Julie Bérubé, None; Frédéric Mouriaux, None; Arnaud de la Fouchardière, None; Solange Landreville, None
  • Footnotes
    Support  Supported by the Fondation des maladies de l’oeil, the Vision Health Research Network (International Networking, Uveal Melanoma Common Infrastructure, postdoctoral scholarship), the Fondation d’ophtalmologie, recherche et développement (postdoctoral scholarship), the Fonds de Recherche du Québec-Santé, and the Canada Foundation for Innovation.
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 3185. doi:
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      Léo PIQUET, Peter Gerges, William Pelletier, Julie Bérubé, Frédéric Mouriaux, Arnaud de la Fouchardière, Solange Landreville; Recruitment and activation of hepatic stellate cells by uveal melanoma cells in a xenograft mouse model. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3185.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Uveal melanoma (UM) spreads to the liver in half of the cases, and the survival rate following the report of metastasis is less than 10% at 2 years. Activated hepatic stellate cells (HSCs) play pivotal roles in the metastatic progression of colorectal and pancreatic cancers. We thus tested the hypothesis that HSCs would provide a suitable microenvironment that will enhance the UM cell invasion using a xenograft mouse model of metastatic UM.

Methods : Fluorescent metastatic UM cell lines H79, MU2F, TJU-UM001 and OMM2.3 were inoculated alone or with human HSCs in the spleen of immunodeficient mice (N=8/group) to generate micro- and macrometastases in the liver in 3-6 weeks. The growth of the hepatic lesions was imaged with an in vivo imaging system. Histological analyses were performed on formalin-fixed paraffin-embedded (FFPE) tissue sections using hematoxylin & eosin and Masson’s trichrome stains, and antibodies against MART-1, α-SMA, Ki67 and CD31 (imaging software: NDP.view 2). We compared our findings with stainings in UM liver metastases from patients treated by partial hepatectomy (N=12).

Results : All UM cell lines, inoculated alone or with human HSCs, spread to the liver as micro- or macrometastases. Furthermore, UM cell lines exhibited various invasive capabilities. Histological analyses of FFPE tissue sections revealed multiple metastasis foci, a significant recruitment of both host and injected human HSCs near the lesions, as well as an increase in extracellular matrix production. Interestingly, activated HSCs surrounding micro- and macrometastasis, as well as desmoplastic areas were also found in patient hepatectomy samples.

Conclusions : The results in both our xenograft model and a cohort of patients are consistent with our hypothesis that HSCs are recruited and activated by UM lesions, thus providing a permissive microenvironment to invasion. Further characterization of the paracrine signaling of activated HSCs and their desmoplastic stroma will be needed to understand how to antagonize these prometastatic contributors.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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