Indoleamine 2,3-dioxygenase activity and l-tryptophan transport in human breast cancer cells

Abstract

The activity and expression of indoleamine 2,3-dioxygenase together with L-tryptophan transport has been examined in cultured human breast cancer cells. MDA-MB-231 but not MCF-7 cells expressed mRNA for indoleamine 2,3-dioxygenase. Kynurenine production by MDA-MB-231 cells, which was taken as a measure of enzyme activity, was markedly stimulated by interferon-gamma (1000 units/ml). Accordingly, L-tryptophan utilization by MDA-MB-231 cells was enhanced by interferon-gamma. 1-Methyl-DL-tryptophan (1 mM) inhibited interferon-gamma induced kynurenine production by MBA-MB-231 cells. Kynurenine production by MCF-7 cells remained at basal levels when cultured in the presence of interferon-gamma. L-Tryptophan transport into MDA-MB-231 cells was via a Na(+)-independent, BCH-sensitive pathway. It appears that system L (LAT1/CD98) may be the only pathway for l-tryptophan transport into these cells. 1-Methyl-D,L-tryptophan trans-stimulated l-tryptophan efflux from MDA-MB-231 cells and thus appears to be a transported substrate of system L. The results suggest that system L plays an important role in providing indoleamine-2,3-dioxygenase with its main substrate, L-tryptophan, and suggest a mechanism by which estrogen receptor-negative breast cancer cells may evade the attention of the immune system.

Indoleamine 2,3-dioxygenase (IDO) expression in lung cancer

“…With the exception of the report of IDO expression by the NSCLC line NCI-H596 by Uyttenhove et al, 5 that was also analyzed in our study, this is the only report in the literature directly showing that IDO mRNA can be constitutively expressed by lung cancer cells. This result is in accordance with similar findings of other investigators regarding the ability of other types of cancer cells, such as colon cancer, 11 ovarian cancer, 12 breast cancer, 13 etc., to produce this immunoregulatory enzyme.…”

“…The difference of histochemically detected IDO expression between NSCLC and SCLC, described by Uyttenhove et al, 5 cannot be supported by our work, as we have examined only one SCLC sample. Possibly, biological factors other than the histological identity of cancer cells, including for example the interferon secreted by the tumor itself, 13,18 control the ability of the tumor cells to express IDO. These factors could also account for the wide variation of IDO expression values detected in all of our samples as well as in other tumor types.…”

In Vivo Uptake and Metabolism of α-[11C]Methyl-l-Tryptophan in Human Brain Tumors

“…Malignant cells are generally believed to have an increased rate of amino-acid transport, presumably due to increased demand for protein synthesis (Isselbacher, 1972;Jager et al, 2001). Alternatively, increased transport of tryptophan to the tumor cell when IDO activity is enhanced may actually diminish the immune response to the tumor, as suggested by studies in human breast cancer cells (Travers et al, 2004).…”

Potential Biomarker of L-type Amino Acid Transporter 1 in Breast Cancer Progression

“…Actively proliferating cancer cells require more nutrients, such as amino acids and glucose, than quiescent cells. With regard to the relationship between LAT1 and breast cancer, there have been only four publications so far reporting the role of LAT1 in two cultured breast cancer cell lines, from Shennan and his colleagues [17][18][19][20].…”