C. Song, Q. Wang, Chang-Cheng Song
Aug 15, 2012
Citations
1
Influential Citations
10
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Journal
International Journal of Cancer
Abstract
Dear Editor, Hemorphin family constitutes a spectrum of bioactive opioid peptides derived from proteolysis of the b, c, d or e chain of hemoglobin. Hemorphin-3 harbors the tripeptide Tyr-ProTrp core sequence of all hemorphins. A sequential degradation of hemoglobin generates a series of structural overlapped peptides with Nand/or C-terminal extensions of TyrPro-Trp. Hemorphin-3 to -7 represent the C-terminal truncations. The hemorphin subfamilies involve N-terminal sequences and identify as hemorphins, V-hemorphins, VV-hemorphins and LVV-hemorphins. Hemoglobin, a specialized hemecontaining protein, exists in erythrocytes and accounts for 98% of intraerythrocyte protein. Erythrocytes finish the synthesis of hemoglobin before ribosomal degradation during the terminal development of reticulocyte. Mature erythrocytes discard their nuclei and get rid of all intracellular compartments in a bid to maximize cellular hemoglobin. Hemoglobin molecules in erythrocytes serve as the principle transport medium of oxygen and carbon dioxide between the lungs and the tissues. Intriguingly, hemoglobin may involve in the forming of molecules to perform a holistic regulation as well. The hemoglobinderived hemorphins steer the cell growth in response to various physiologic and pathological changes via fine regulation of their intracellular concentration. Hemoglobin decline is known as a sign of malignant diseases. Around 40% cancer patients exhibit prediagnostic anemia. A previous report in this journal illuminated whether hemoglobin concentration was in connection with various malignant diseases at preclinical duration. The investigation was carried out in a large cohort of blood donors. The result showed no significant change in hemoglobin concentration between breast cancer cases and the respective controls at any time. Erythrocytes manifest a preferential production and excretion of hemorphin-7 (Tyr-Pro-Trp-Thr-Gln-Arg-Phe). Cohen et al. measured the hemorphin-7 in serums of 62 breast cancer patients and 25 healthy controls. The serum levels of hemorphin-7 are significantly lower in breast cancer patients than those in controls. However, the serum content of hemorphin-7 in metastasic breast cancer was not notably different when compared with nonmetastasic breast carcinoma. They proposed the decrease of serum hemorphin-7 in breast cancer patients was due to its incremental degradation by cathepsin B. Nevertheless, we regard plasma proteasome as a probable candidate for the hydrolysis of hemorphin-7. Proteasome, a conserved multicatalytic proteinase complex, is in charge of protein degradation. In various cancers, proteasome exhibits an increased activity of blood plasmsa and malignant tissues. Hoffmann et al. recently reported the different levels of plasmsa 20S proteasome in 224 nonmetastatic breast cancer patients and 50 healthy donors. They determined the circulating proteasome by immunoassay and showed a significantly higher concentration in patients with breast carcinoma (397.5 ng/ml) than in healthy subjects (305 ng/ml). It was logical to suggest that the reduction level of serum hemorphin-7 in breast cancer might be due to the increase of circulating proteasome. The catalytic b1, b2 and b5 subunit of proteasome manifests caspase-like, trypsin-like and chymotrypsinlike activities, respectively. The chymotrypsin like-protease rather than trypsin-like enzyme may participate in the processing of hemorphins as cleavage sites contain hydrophobic residues. We speculated hemorphin-7 as a substrate for plasma proteasome because of its correspondence with the plasmsa proteasomal activity. Hemorphin-7 exhibited no correlation to patients’ age and the metastasic state of breast cancer. It is rapid and convenient to detect the serum hemorphin-7 by enzyme linked immunosorbent assay. Thus, hemorphin-7 would represent a probable biomarker in breast cancer. In addition, hemorphin participates in the anticancer action on breast carcinoma by several mechanisms. For instance, hemorphin displayed the inhibitory effect on breast cancer by means of its antiproliferative and cytolytic activity. The Tyr-Pro-Trp sequence of hemorphin-3 is the primary structure of the hitherto known hemorphins and demonstrates the indispensable role in binding to land d-opiate receptors as a minimum. Hemorphins function as ligands of opiate receptors with their preference to receptor subtypes, such as hemorphin-4 is in favor of l-, dand j-receptors, hemorphin-7 desires to l-receptor and hemorphin-6 presents extra affinity for r-receptor. VV-hemorphins and LVV-hemorphins preferentially interact with dand j-receptors by analogs affinity. VV-hemorphin-5, also known as valorphin, resides in position 33–39 of the b, c, d or e chain of human hemoglobin. As an opiate ligand, VV-hemorphin-5 binds the dand j-opiate receptors and plays the roles of endogenous opiate peptide in vivo. The available literature data speak of the antitumor effect of VV-hemorphin-5 both in vitro and Le tt er to th e E di to r