Natural variations of copper and sulfur stable isotopes in blood of hepatocellular carcinoma patients.
Proc Natl Acad Sci U S A
; 112(4): 982-5, 2015 Jan 27.
Article
em En
| MEDLINE
| ID: mdl-25583489
ABSTRACT
The widespread hypoxic conditions of the tumor microenvironment can impair the metabolism of bioessential elements such as copper and sulfur, notably by changing their redox state and, as a consequence, their ability to bind specific molecules. Because competing redox state is known to drive isotopic fractionation, we have used here the stable isotope compositions of copper ((65)Cu/(63)Cu) and sulfur ((34)S/(32)S) in the blood of patients with hepatocellular carcinoma (HCC) as a tool to explore the cancer-driven copper and sulfur imbalances. We report that copper is (63)Cu-enriched by â¼0.4 and sulfur is (32)S-enriched by â¼1.5 in the blood of patients compared with that of control subjects. As expected, HCC patients have more copper in red blood cells and serum compared with control subjects. However, the isotopic signature of this blood extra copper burden is not in favor of a dietary origin but rather suggests a reallocation in the body of copper bound to cysteine-rich proteins such as metallothioneins. The magnitude of the sulfur isotope effect is similar in red blood cells and serum of HCC patients, implying that sulfur fractionation is systemic. The (32)S-enrichment of sulfur in the blood of HCC patients is compatible with the notion that sulfur partly originates from tumor-derived sulfides. The measurement of natural variations of stable isotope compositions, using techniques developed in the field of Earth sciences, can provide new means to detect and quantify cancer metabolic changes and provide insights into underlying mechanisms.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Enxofre
/
Carcinoma Hepatocelular
/
Cobre
/
Microambiente Tumoral
/
Neoplasias Hepáticas
Limite:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article