Overexpression of L-Type Amino Acid Transporter 1 (LAT1) and 2 (LAT2): Novel Markers of Neuroendocrine Tumors

Abstract

Background6-18F-fluoro-L-3,4-dihydroxyphenylalanine (18F-FDOPA) PET is a useful tool in the clinical management of pheochromocytoma (PHEO) and medullary thyroid carcinoma (MTC). 18F-FDOPA is a large neutral amino acid biochemically resembling endogenous L-DOPA and taken up by the L-type amino acid transporters (LAT1 and LAT2). This study was conducted to examine the expression of the LAT system in PHEO and MTC.MethodsReal-time PCR and Western blot analyses were used to assess LAT1 and LAT2 gene and protein expression in 32 PHEO, 38 MTC, 16 normal adrenal medulla and 15 normal thyroid tissue samples. Immunohistochemistry method was applied to identify the proteins’ subcellular localization.ResultsLAT1 and LAT2 were overexpressed in both PHEO and MTC by comparison with normal tissues. LAT1 presented a stronger induction than LAT2, and their greater expression was more evident in PHEO (15.1- and 4.1-fold increases, respectively) than in MTC (9.9- and 4.1-fold increases, respectively). Furthermore we found a good correlation between LAT1/2 and GLUT1 expression levels. A positive correlation was also found between urinary noradrenaline and adrenaline levels and LAT1 gene expression in PHEO. The increased expression of LAT1 is also confirmed at the protein level, in both PHEO and MTC, with a strong cytoplasmic localization.ConclusionsThe present study is the first to provide experimental evidence of the overexpression in some NET cancers (such as PHEO or MTC) of L-type amino acid transporters, and the LAT1 isoform in particular, giving the molecular basis to explain the increase of the DOPA uptake seen in such tumor cells.

Expression profile of the amino acid transporters SLC 7A5, SLC 7A7, SLC 7A8 and the enzyme TDO 2 in basal cell carcinoma

“…Increased expression of SLC7A5 in tumours is suggested to be of importance for cell growth and survival and the effects of inhibitory drugs are being evaluated for cancer treatment . SLC7A8 is less well studied in cancer, but found to be overexpressed in neuroendocrine tumours . We found both SLC7A5 and SLC7A8 overexpression in BCC (Figs and ), verified by gene and protein analysis, which supports previous reports of altered expression in tumour cells.…”

Incidental Accumulation of Fluciclovine in Neuroendocrine Tumour in a Patient with Oncological Duplicity

“…It is overexpressed in some NET, such as pheochromocytoma, medullary thyroid carcinoma, and NET of the lungs. Its overexpression was proven in many types of solid tumours [11][12][13]. Our patient was diagnosed with grade I NET; however, in a study by Kaira et al [13], all 10 patients diagnosed with grade I NET of the lung did not express LAT-1.…”

Tumor-Specific Peptide, Selected from a Phage Peptide Library, Enhances Antitumor Activity of Lactaptin

“…The development of novel antitumor drugs depends, on the one hand, on the ability to influence cellular processes and pathways, which differ between cancer and normal cells, and, on the other hand, on the ability of targeting agents to effectively deliver drugs to the tumor. The latter is possible due to multiple genetic and epigenetic changes that occur during oncogenesis and lead to changes in the proteomic profile of the cancer cell [ 12 – 14 ]. Changes in the type, number and location of receptors results in the formation of a unique topographic phenotype of the cell surface.…”