Peptide name : MHC Class I chain-related protein

Source/Organism : Human

Linear/Cyclic : Not found

Chirality : Not found

Peptide length: 383

C-terminal modification: Not found

N-terminal modification : Not found

Non-natural peptide information: None

Assay type : WST-8 assay

Assay time : 24h

Activity : MIC : >5 µg/mL

Cell line : PLC/PRF/5

Cancer type : Hepatocellular carcinoma

Other activity : Not found

Amino acid composition bar chart :

Molecular mass : 42891.8801 Dalton

Aliphatic index : 0.750

Instability index : 49.7962

Hydrophobicity (GRAVY) : -0.409

Isoelectric point : 6.2388

Charge (pH 7) : -5.1329

Aromaticity : 0.083

Molar extinction coefficient (cysteine, cystine): (62910, 63410)

Hydrophobic/hydrophilic ratio : 0.94416243

hydrophobic moment : -0.192

Missing amino acid : None

Most occurring amino acid : L

Most occurring amino acid frequency : 37

Least occurring amino acid : M

Least occurring amino acid frequency : 9

Secondary structure fraction (Helix, Turn, Sheet): (0.2, 0.2, 0.3)

SMILES Notation: 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1 : Kohga K, et al. Anticancer chemotherapy inhibits MHC class I-related chain a ectodomain shedding by downregulating ADAM10 expression in hepatocellular carcinoma. Cancer Res. 2009; 69:8050-7. doi: 10.1158/0008-5472.CAN-09-0789

Paper title : Anticancer chemotherapy inhibits MHC class I-related chain a ectodomain shedding by downregulating ADAM10 expression in hepatocellular carcinoma.

Doi : https://doi.org/10.1158/0008-5472.CAN-09-0789

Abstract : MHC class I-related chain A (MICA) is a ligand for the NKG2D-activating immunoreceptor that mediates activation of natural killer (NK) cells. The ectodomain of MICA is shed from tumor cells, which may be an important means of evading antitumor immunity. We previously reported that patients with hepatocellular carcinoma (HCC) display high levels of soluble MICA in circulation, which could be downregulated by chemotherapy. The present study shows that anti-HCC drugs suppress MICA ectodomain shedding by inhibiting expression of a disintegrin and metalloproteinase 10 (ADAM10). Both ADAM10 and CD44, a typical substrate of the ADAM10 protease, were expressed in human HCC tissues and HCC cells but not in normal liver tissues or cultured hepatocytes. Small interfering RNA-mediated knockdown experiments revealed that ADAM10 is a critical sheddase for both MICA and CD44 in HCC cells. Of interest is the finding that epirubicin clearly downregulated ADAM10 expression and MICA shedding in HCC cells; its suppressive effect on MICA shedding was abolished in ADAM10-depleted cells. Epirubicin treatment also enhanced the NKG2D-mediated NK sensitivity of HCC cells. Patients with HCC had significantly higher levels of serum-soluble CD44, which correlated well with serum-soluble MICA levels, thus suggesting a close link between ADAM10 activity and MICA shedding in these patients. Soluble MICA and CD44 levels were downregulated with a significant correlation in patients treated by transarterial chemoembolization using epirubicin. In conclusion, anticancer drugs can modulate expression of ADAM10, which is critically involved in MICA ectodomain shedding. Epirubicin therapy may have a previously unrecognized effect on antitumor immunity in HCC patients.