Uncovering the role of lysyl oxidase-like 2 (LOXL2) in rhabdomyosarcoma

Introduction: Rhabdomyosarcoma (RMS) is the most common soft tissue malignancy in childhood and adolescence that originates as a consequence of regulatory disruption in the growth and differentiation of muscle precursor cells. Previous results of our group deciphered the epigenetic profiling of RMS, compared to healthy tissue, revealing the hypomethylation of a potential enhancer of LOXL2. LOXL2 is an amine oxidase that catalyzes the covalent crosslinking of collagen and elastin in the extracellular matrix. Apart from its traditional role, novel functions have been attributed to LOXL2 related to tumor progression.

Methods: Infinium 450k Illumina methylation array of RMS cell lines and patients. Western blot, qRT-PCR, clonogenic, proliferation and migration assays.

Results: We first confirmed the overexpression of LOXL2 in RMS cell lines compared to other sarcoma cells by qRT-PCR and Western blot. Moreover, we characterized the neoplastic phenotype after silencing LOXL2 expression in RH4 cell line. LOXL2 silencing resulted in a decrease in the clonogenic capacity, proliferation and cell migration. On the other hand, gain of function experiments in LOXL2 under-expressed cells (RH28) using wild type or mutated (catalytically inactive) constructs of LOXL2 will be crucial to further explore its role in RMS.

Conclusion: Our preliminary results suggest an oncogenic role of LOXL2 in RMS.