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As the cancer-related functions of both, Lysyl Oxidase (LOX) and Lysyl Oxidase Like 2 (LOXL2), have not yet been investigated in squamous cell carcinoma of the head and neck (HNSCC), the mRNA levels of LOX and LOXL2, respectively, in malignantly transformed cell lines and malignant tissue samples of different graded and staged HNSCC were examined by reverse transcription – polymerase chain reaction (RT-PCR). In this study we showed that the LOX-mRNA level in both cell lines and tissues of HNSCC was markedly reduced as opposed to benign keratinocyte cell lines and mucosal tissue samples of the upper aerodigestive tract. Similar results were shown for LOXL2-mRNA levels in cell lines, whereas no reduction of LOXL2-mRNA levels was found in the malignantly transformed tissues. These findings support the presumption of LOX being involved in tumor suppressive processes and of also LOXL2 playing a role in malignant transformation. Herewith the possible role of LOX and LOXL2 in tumor suppression might be shown in HNSCC for the first time, whereas the tumor suppressive function of LOX seems to be higher compared to the one of LOXL2. Thus, LOXL2 might share some functions of LOX, without being able to completely substitute LOX. Progressive loss or specific patterns of LOX and LOXL2 expression in biopsy material may be of prognostic significance for patients with HNSCC. Both LOX genes should be considered as potential tumor-suppressor genes or at least components of a tumor suppressor pathway for HNSCC and, therefore, as a target for further molecular therapeutic concepts.