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

Abstract

Ovarian cancer remains one of the most fatal cancers due to a 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, as well as metastatic spread. The aim of this study was to analyze the effect of lumican on tumor growth of murine ovarian epithelial cancer. C57BL/6 wild type mice (n = 12) and lumican-deficient mice (n = 10) were subcutaneously injected with murine ovarian epithelial carcinoma ID8 cells, and then 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 anti-lumican, anti-αv integrin, anti-CD31 and anti-cyclin D1 antibodies, and then further examined by label-free infrared spectral imaging (IRSI), second harmonic generation (SHG) and Picrosirius red staining. The IR tissue images allowed for the identification of different ECM tissue regions of the skin and the ovarian tumor. Moreover, IRSI showed a good correlation with αv integrin immunostaining and collagen organization within the tumor. Our results demonstrate that lumican inhibits ovarian cancer growth mainly by altering collagen fibrilogenesis.

Lumican is a potential predictor on the efficacy of concurrent chemoradiotherapy in cervical squamous cell carcinoma

“…Li et al [ 21 ] discovered that extracellular LUM enhances chemotherapy cytotoxicity in PDAC cells through reduced AMPK activity and inhibition of chemotherapeutic agent-induced autophagy. Nizet et al [ 22 ] showed that LUM primarily inhibits ovarian cancer growth by altering collagen fibrillogenesis. LUM expression differs among tumors and is reported as a reference for tumor prognosis, but its association with tumor progression and treatment resistance varies across tumors [ [22] , [23] , [24] ].…”

“…Nizet et al [ 22 ] showed that LUM primarily inhibits ovarian cancer growth by altering collagen fibrillogenesis. LUM expression differs among tumors and is reported as a reference for tumor prognosis, but its association with tumor progression and treatment resistance varies across tumors [ [22] , [23] , [24] ]. No studies have examined the efficacy of LUM and CCRT in CESC.…”