Laminin Cl expression by uterine carcinoma cells is associated with tumor progression

Objectives. Molecular markers associated with tumor progression in uterine carcinoma are poorly defined. In this study, we determine whether upregulation of LAMC1, a gene encoding extracellular matrix protein, laminin gamma 1, is associated with various uterine carcinoma subtypes and stages of tumor progression. Methods. An analysis of the immunostaining patterns of laminin gamma 1 in normal endometrium, atypical hyperplasia, and a total of 150 uterine carcinomas, including low-grade and high-grade endometrioid carcinomas, uterine serous and clear cell carcinoma, was performed. Clinicopathological correlation was performed to determine biological significance. The Cancer Genome Atlas (TCGA) data set was used to validate our results. Results. As compared to normal proliferative and secretory endometrium, for which laminin immunoreactivity was almost undetectable, increasing laminin C1 staining intensity was observed in epithelial cells from atypical hyperplasia to low-grade endometrioid to high-grade endometrioid carcinoma, respectively. Laminin gamma 1 expression was significantly associated with FIGO stage, myometrial invasion, cervical/adnexal involverrient, angiolymphatic invasion and lymph node metastasis. Similarly, analysis Of the endometrial carcinoma data set from TCGA revealed that LAMC1 transcript levels were higher in high-grade than those in low-grade endometrioid carcinoma. Silencing LAMC1 expression by siRNAs in a high-grade endometrioid carcinoma cell line did not affect its proliferative activity but significantly suppressed cell motility and invasion in vitro. Conclusions. These data suggest that laminin gamma 1 may contribute to the development and progression of uterine carcinoma, likely through enhancing tumor cell motility and invasion. Laminin gamma 1 warrants further investigation regarding its role as a biomarker and therapeutic target in uterine carcinoma. (C) 2015 Elsevier Inc. All rights reserved.