Novel fusion proteins of interferon alpha2b cause growth inhibition and induce JAK-STAT signaling in melanoma.
Melanoma is an aggressive form of skin cancer with high occurrence in the United States. Interferon alpha2b (IFNalpha2b/IFNalpha2) has been used in high doses to treat melanoma. However, problems associated with small molecule therapeutics such as with IFN treatment include small molecular size, degradation by serum proteases, and rapid kidney clearance. Pegylation has been used to overcome this, but in itself possesses a host of other issues such as decrease receptor binding, nonspecific chemical derivatization, low overall yields, and additional purification steps. An alternative to this produces IFN as arabinogalactan fusion proteins in plant cells. These IFN analogs bind to IFN receptors and follow the IFN-induced Janus Kinase 1-signal transducers and activators of transcription signaling pathway. Here, we show that these fusion proteins of higher molecular weight also cause similar growth inhibition and affect cell cycle distribution in melanoma cells M92-047 and SK MEL-28. Lastly, the fusion proteins increased translation of 2'5'-oligo adenylate synthetase and Protein Kinase R, known IFN-induced proteins, showing similar downstream signaling as native recombinant IFNalpha2.
Fernandes
Elroy
E
Department of Chemistry and Biochemistry, Ohio University, Athens, OH, USA.
Soans
Eroica
E
Xu
Jianfeng
J
Kieliszewski
Marcia
M
Evans
Susan C
SC
D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D016503:Drug Delivery Systems; D005685:Galactans / Q000235:genetics / Q000378:metabolism*; D018628:Gene Dosage / Q000235:genetics; D006801:Humans; D007167:Immunotherapy; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000235:genetics / Q000378:metabolism*; D053613:Janus Kinase 1 / Q000235:genetics / Q000378:metabolism; D008545:Melanoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D015202:Protein Engineering; D055550:Protein Stability / Q000187:drug effects; D017471:Receptors, Interferon / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D019892:eIF-2 Kinase / Q000378:metabolism
D005685:Galactans; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D017471:Receptors, Interferon; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D050791:STAT Transcription Factors; D053613:Janus Kinase 1; D019892:eIF-2 Kinase; D015088:2',5'-Oligoadenylate Synthetase; C005653:arabinogalactan