Assessment of Ovarian Tumor Growth in Wild-Type and Lumican-Deficient Mice: Insights Using Infrared Spectral Imaging, Histopathology, and Immunohistochemistry

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Nizet, Pierre | Untereiner, Valérie | Sockalingum, Ganesh, D | Proult, Isabelle | Terryn, Christine | Jeanne, Albin | Nannan, Lise | Boulagnon-Rombi, Camille | Sellier, Christèle | Rivet, Romain | Ramont, Laurent | Brézillon, Stéphane

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International audience. URCAnim Ovarian cancer remains one of the most fatal cancers because of lack of robust screening methods of detection at early stages. Extracellular matrix (ECM) mediates interactions between cancer cells and their microenvironment via specific molecules. Lumican, a small leucine-rich proteoglycan (SLRP), maintains ECM integrity and inhibits both melanoma primary tumor development and metastatic spreading. The aim of this study was to analyze the effect of lumican on tumor growth of murine ovarian epithelial carcinoma. C57BL/6 wild type mice (n=12) and lumican-deficient mice (n=10) were subcutaneously injected with murine ovarian epithelial carcinoma ID8 cells and sacrificed after 18 days. Analysis of tumor volumes demonstrated an inhibitory effect of endogenous lumican on ovarian tumor growth. The ovarian primary tumors were subjected to histological and immunohistochemical staining using antilumican, anti-αv integrin, anti-CD31 and anti-cyclin D1 antibodies, and further examined by label-free infrared spectral imaging (IRSI), second harmonic generation (SHG) and Picrosirius Red staining. The IR tissue images identified different ECM tissue regions of the skin and the ovarian tumor. Moreover, IRSI showed a good correlation of αv integrin immunostaining and collagen organization within the tumor. Our results demonstrate for the first time that lumican inhibits the growth of ovarian cancer mainly by altering collagen organization and distribution.

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