Increased expression of LAT1 in basal cell carcinoma: implications for tumour cell survival.

BACKGROUND

Basal cell carcinoma (BCC) is the most common type of cancer in fair-skinned individuals worldwide. Altered metabolism is a hallmark of cancer, and a growing body of evidence has shown increased expression of the large neutral amino acid transporter small subunit 1 (LAT1) in several types of cancers, including BCC. However, the mechanisms behind changed LAT1 expression in BCC are largely unknown.

AIM

To describe the protein expression of LAT1 and its colocalization with LAT2, and to examine LAT1 in association with BCC tumour biology characteristics such as cell proliferation, apoptosis and hypoxia.

METHODS

Immunofluorescence stains were used on formalin-fixed, paraffin-embedded tissue samples (n = 14) from excised BCCs, and their protein-staining patterns were examined.

RESULTS

There was no correlation between expression of LAT1 and LAT2, and the colocalization was low. Compared with normal epidermis, there was significantly higher expression in BCC tissue of the proliferation markers topoisomerase IIα (P < 0.01) and Ki-67 (P = 0.01). The fraction of LAT1-expressing cells in BCC tissue was significantly (P < 0.01) inversely correlated with the fraction of proliferative active tumour cells. Cleaved caspase-3 was significantly (P = 0.02) increased in tumour areas with high LAT1 expression.

CONCLUSIONS

The present study shows that LAT1 is not usually expressed by proliferating BCC cells. The morphological localization suggests that tumour cells use LAT1 to adapt to environmental changes such as starvation and/or hypoxia. These findings could have implications for future development of LAT1-inhibitory BCC treatments.

© 2021 The Authors. Clinical and Experimental Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.