Elsevier

Life Sciences

Volume 65, Issue 21, 15 October 1999, Pages 2223-2231
Life Sciences

Increased expression of peripheral benzodiazepine receptors and diazepam binding inhibitor in human tumors sited in the liver

https://doi.org/10.1016/S0024-3205(99)00487-7Get rights and content

Abstract

The peripheral benzodiazepine receptor system triggers intracellular metabolic events and has been associated with cell proliferation. Its endogenous ligand, the diazepam binding inhibitor, contributes to steroidogenesis by promoting cholesterol delivery to the inner mitochondrial membrane. The present study was undertaken to verify whether this system is altered in tumors sited in the liver. Peripheral benzodiazepine receptors and diazepam binding inhibitor were studied using immunocytochemistry and in situ hybridization in 9 human tumors sited in the liver, in liver hyperplasia, cirrhotic nodular regeneration, intestinal adenocarcinoma and in surrounding non-tumoral tissue. Immunocytochemical staining and in situ hybridization demonstrated that peripheral benzodiazepine receptors and diazepam binding inhibitor were more prominently expressed in neoplastic cells than in non-tumoral tissue. They were present in the same cells, suggesting that diazepam binding inhibitor may act in an intracrine manner in these cells. Higher peripheral benzodiazepine receptors and diazepam binding inhibitor expression in tumor cells suggest an implication of this system in the metabolism of neoplastic cells. Furthermore the evaluation of peripheral benzodiazepine receptor and diazepam binding inhibitor expression might be useful in evaluating malignancy and in diagnostic approaches of tumors in liver tissue.

References (35)

  • R.R.H. Anholt et al.

    J. Biol. Chem.

    (1986)
  • M.J. Woods et al.

    Biochemical Pharmacology

    (1996)
  • B.O. Oke et al.

    Mo. Cell. Endocrinol.

    (1992)
  • E. Costa et al.

    Life Sci.

    (1991)
  • K.E. Krueger

    Biochem. Biophys. Acta

    (1995)
  • K.E. Krueger et al.

    J. Biol. Chem.

    (1990)
  • V. Papadopoulos et al.

    J. Biol. Chem.

    (1991)
  • E. Slobodyansky et al.

    B. Regul. Pept.

    (1994)
  • M. Pawlikowski et al.

    Life Sci.

    (1987)
  • P. Carayon et al.

    Blood

    (1996)
  • I. Venturini et al.

    Life Sci.

    (1998)
  • I. Venturini et al.

    Regul. Pept.

    (1998)
  • R. Van Hillegersberg et al.

    Gastroenterology

    (1992)
  • A. Guidotti et al.

    Pharmacology

    (1979)
  • J.F. Tallman et al.

    Annu. Rev. Neurosci.

    (1985)
  • C. Braestrup et al.
  • L. Antkiewicz-Michaluk et al.

    Mol. Pharmacol.

    (1988)
  • Cited by (59)

    • Metal complexes targeting the Translocator Protein 18 kDa (TSPO)

      2017, Coordination Chemistry Reviews
      Citation Excerpt :

      Moreover, heterogeneous cell type-specific TSPO expression has been found in several tissues [7,8] and subcellular localization studies have demonstrated that TSPO is localized primarily on the outer mitochondrial membrane [7,9,10] but also in Golgi apparatus, lysosomes and peroxisomes [11], and on plasma membrane [12]. Interestingly, TSPO is overexpressed in a variety of tumors (e.g., certain brain tumors, ovarian cancer, liver tumors, breast carcinoma, colorectal cancer, etc.) and its expression appears to be related to the degree of tumor malignancy [13–16]. In addition, TSPO is overexpressed on activated microglial cells localized in lesioned brain areas of patients with neurodegenerative or neuroinflammatory diseases like Alzheimer’s disease, Huntington’s disease, and multiple sclerosis [17,18].

    • Long-chain acyl-CoA esters in metabolism and signaling: Role of acyl-CoA binding proteins

      2015, Progress in Lipid Research
      Citation Excerpt :

      A number of external cues have been shown to increase ACBP expression in selected areas of rat brain, including acute stress [187,188], psychological but not physical stress [189], alcohol intake [190–193], nicotine [194–196], diazepam [197,198], continuous treatment with morphine [199], butanol [200] and N-methyl-d-aspartate (NMDA) [201]. Moreover, ACBP levels are also increased in liver, ovarian and brain tumors [202–205] and extraordinarily found in urine after chemotherapy of gall bladder cancer patients [206]. The expression level of the mammalian ACBP is also affected by feeding status.

    • Secretome protein signature of human gastrointestinal stromal tumor cells

      2015, Experimental Cell Research
      Citation Excerpt :

      By comparing the stimulated groups with the control group we revealed subsets of proteins being significantly released upon stimulation. In fact, the majority of the significantly elevated secretory proteins in the thapsigargin group (Table 2) have already been acknowledged in other tumor types, for example; trypsin and PEA-15 in colon cancers [54,55], RNA-binding protein FUS (fused in sarcoma) in myxoid liposarcoma [56], calpain small subunit 1, insulin-like growth factor-binding protein 7, and Acyl-CoA-binding protein in hepatocellular carcinomas [57–59], proteasome subunit alpha type-3 in esophageal cancer [60], inter-alpha-trypsin inhibitor heavy chain H4, fibulin-1, and protein CDV3 homolog in breast cancer [61–63], Apo A-I in ovarian cancer [64], Peroxiredoxin-5 in human lung carcinoma cells [65], glutathione S-transferase Mu 3 in gastric cancer [66], and neutral alpha-glucosidase AB in head and neck cancer [67]. It is also noteworthy that blocking the mutated c-KIT protein with imatinib radically changed the protein release pattern (Tables 2 and 4, Fig. 2).

    View all citing articles on Scopus
    View full text