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Open AccessArticle

Synergic Interactions Between Hepatic Stellate Cells and Uveal Melanoma in Metastatic Growth

1
Faculté de médecine, Université Laval, Quebec City, QC G1V 0A6, Canada
2
Centre de recherche du CHU de Québec-Université Laval, Quebec City, QC G1S 4L8, Canada
3
Centre de recherche sur le cancer de l’Université Laval, Quebec City, QC G1R 3S3, Canada
4
Centre de recherche en organogénèse expérimentale de l’Université Laval/LOEX, Quebec City, QC G1J 1Z4, Canada
*
Author to whom correspondence should be addressed.
Equal contribution.
Cancers 2019, 11(8), 1043; https://doi.org/10.3390/cancers11081043
Received: 26 June 2019 / Revised: 19 July 2019 / Accepted: 22 July 2019 / Published: 24 July 2019
(This article belongs to the Special Issue Uveal Melanoma)
Uveal melanoma (UM) is a malignant intraocular tumor that spreads to the liver in half of the cases. Since hepatic cells could play a role in the therapeutic resistance of metastatic UM, the purpose of our study was to investigate the pro-invasive role of hepatic stellate cells (HSteCs) in metastatic UM at the micro- and macro-metastatic stages. We first performed an immunostaining with the alpha-smooth muscle actin (αSMA) to localize activated HSteCs in UM liver macro-metastases from four patients. Their accumulation of collagen was assessed with Masson’s Trichrome stain. Next, we inoculated metastatic UM cells alone or with human HSteCs in triple-immunodeficient mice, in order to determine if HSteCs are recruited as early as the micro-metastatic stage. The growth of metastatic foci was imaged in the liver by ex vivo fluorescence imaging. Histological analyses were performed with Masson’s Trichrome and Picrosirius Red stains, and antibodies against Melan-A and αSMA. The collagen content was measured in xenografts by quantitative polarization microscopy. In patient hepatectomy samples, activated HSteCs and their pathological matrix were localized surrounding the malignant lesions. In the mouse xenograft model, the number of hepatic metastases was increased when human HSteCs were co-inoculated. Histological analyses revealed a significant recruitment of HSteCs near the micro/macrolesions, and an increase in fibrillar collagen production. Our results show that HSteCs can provide a permissive microenvironment and might increase the therapeutic resistance of metastatic UM. View Full-Text
Keywords: metastatic uveal melanoma; hepatic stellate cells; xenografts; fibrogenesis; histopathological growth patterns; quantitative polarization microscopy metastatic uveal melanoma; hepatic stellate cells; xenografts; fibrogenesis; histopathological growth patterns; quantitative polarization microscopy
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MDPI and ACS Style

Piquet, L.; Dewit, L.; Schoonjans, N.; Millet, M.; Bérubé, J.; Gerges, P.R.A.; Bordeleau, F.; Landreville, S. Synergic Interactions Between Hepatic Stellate Cells and Uveal Melanoma in Metastatic Growth. Cancers 2019, 11, 1043. https://doi.org/10.3390/cancers11081043

AMA Style

Piquet L, Dewit L, Schoonjans N, Millet M, Bérubé J, Gerges PRA, Bordeleau F, Landreville S. Synergic Interactions Between Hepatic Stellate Cells and Uveal Melanoma in Metastatic Growth. Cancers. 2019; 11(8):1043. https://doi.org/10.3390/cancers11081043

Chicago/Turabian Style

Piquet, Léo; Dewit, Louise; Schoonjans, Nathan; Millet, Martial; Bérubé, Julie; Gerges, Peter R.A.; Bordeleau, François; Landreville, Solange. 2019. "Synergic Interactions Between Hepatic Stellate Cells and Uveal Melanoma in Metastatic Growth" Cancers 11, no. 8: 1043. https://doi.org/10.3390/cancers11081043

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