Human IGF1 pro-forms induce breast cancer cell proliferation via the IGF1 receptor
被引:35
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作者:
De Santi, Mauro
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Univ Urbino Carlo Bo, Dept Biomol Sci, Hyg Unit, Via S Chiara 27, I-61029 Urbino, PU, ItalyUniv Urbino Carlo Bo, Dept Biomol Sci, Hyg Unit, Via S Chiara 27, I-61029 Urbino, PU, Italy
De Santi, Mauro
[1
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Annibalini, Giosue
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机构:
Univ Urbino Carlo Bo, Dept Biomol Sci, Exercise & Hlth Sci Unit, Via S Chiara 27, I-61029 Urbino, PU, ItalyUniv Urbino Carlo Bo, Dept Biomol Sci, Hyg Unit, Via S Chiara 27, I-61029 Urbino, PU, Italy
Annibalini, Giosue
[2
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Barbieri, Elena
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机构:
Univ Urbino Carlo Bo, Dept Biomol Sci, Exercise & Hlth Sci Unit, Via S Chiara 27, I-61029 Urbino, PU, ItalyUniv Urbino Carlo Bo, Dept Biomol Sci, Hyg Unit, Via S Chiara 27, I-61029 Urbino, PU, Italy
Barbieri, Elena
[2
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Villarini, Anna
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机构:
Fdn IRCCS Ist Nazl Tumori, Dept Prevent & Predict Med, Epidemiol & Prevent Unit, Milan, ItalyUniv Urbino Carlo Bo, Dept Biomol Sci, Hyg Unit, Via S Chiara 27, I-61029 Urbino, PU, Italy
Villarini, Anna
[3
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Vallorani, Luciana
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Univ Urbino Carlo Bo, Dept Biomol Sci, Exercise & Hlth Sci Unit, Via S Chiara 27, I-61029 Urbino, PU, ItalyUniv Urbino Carlo Bo, Dept Biomol Sci, Hyg Unit, Via S Chiara 27, I-61029 Urbino, PU, Italy
Vallorani, Luciana
[2
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Contarelli, Serena
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Univ Urbino Carlo Bo, Dept Biomol Sci, Exercise & Hlth Sci Unit, Via S Chiara 27, I-61029 Urbino, PU, ItalyUniv Urbino Carlo Bo, Dept Biomol Sci, Hyg Unit, Via S Chiara 27, I-61029 Urbino, PU, Italy
Contarelli, Serena
[2
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Berrino, Franco
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Fdn IRCCS Ist Nazl Tumori, Dept Prevent & Predict Med, Epidemiol & Prevent Unit, Milan, ItalyUniv Urbino Carlo Bo, Dept Biomol Sci, Hyg Unit, Via S Chiara 27, I-61029 Urbino, PU, Italy
Berrino, Franco
[3
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Stocchi, Vilberto
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Univ Urbino Carlo Bo, Dept Biomol Sci, Exercise & Hlth Sci Unit, Via S Chiara 27, I-61029 Urbino, PU, ItalyUniv Urbino Carlo Bo, Dept Biomol Sci, Hyg Unit, Via S Chiara 27, I-61029 Urbino, PU, Italy
Stocchi, Vilberto
[2
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Brandi, Giorgio
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Univ Urbino Carlo Bo, Dept Biomol Sci, Hyg Unit, Via S Chiara 27, I-61029 Urbino, PU, ItalyUniv Urbino Carlo Bo, Dept Biomol Sci, Hyg Unit, Via S Chiara 27, I-61029 Urbino, PU, Italy
Brandi, Giorgio
[1
]
机构:
[1] Univ Urbino Carlo Bo, Dept Biomol Sci, Hyg Unit, Via S Chiara 27, I-61029 Urbino, PU, Italy
[2] Univ Urbino Carlo Bo, Dept Biomol Sci, Exercise & Hlth Sci Unit, Via S Chiara 27, I-61029 Urbino, PU, Italy
[3] Fdn IRCCS Ist Nazl Tumori, Dept Prevent & Predict Med, Epidemiol & Prevent Unit, Milan, Italy
IGF1;
pro-forms;
Breast cancer;
receptor;
GROWTH FACTOR-IA;
MGF E PEPTIDE;
MONOCLONAL-ANTIBODIES;
EXPRESSION;
MUSCLE;
ISOFORMS;
PROHORMONE;
D O I:
10.1007/s13402-015-0263-3
中图分类号:
R73 [肿瘤学];
学科分类号:
100214 ;
摘要:
IGF1 is a key regulator of tissue growth and development and has been implicated in the initiation and progression of various cancers, including breast cancer. Through IGF1 mRNA splicing different precursor pro-peptides, i.e., the IGF1Ea, IGF1Eb and IGF1Ec pro-forms, are formed whose biological roles in the pathogenesis of breast cancer have not been established yet. The objective of this study was to assess the biological activity of the IGF1 pro-forms in human breast cancer-derived cells. The different IGF1 pro-forms were generated through transient transfection of HEK293 cells with the respective vector constructs. The resulting conditioned media were applied in vitro to MCF7, T47D and ZR751 breast cancer-derived cell cultures. The recombinant human IGF1 pro-forms were also tested for their binding affinity to an anti-IGF1 specific antibody by immunoprecipitation. To determine whether the IGF1 pro-forms induce cell proliferation, mature IGF1 was neutralised in HEK293-derived conditioned media. We found that the IGF1 pro-forms were the only forms that were produced intra-cellularly, whereas both mature IGF1 and the IGF1 pro-forms were detected extra-cellularly. We also found that E peptides can impair the IGF1 pro-form binding affinity for the anti-IGF1 antibody and, thus, hamper an accurate measurement of the IGF1 pro-forms. Additionally, we found that the IGF1 antibody can completely inhibit IGF1-induced breast cancer cell proliferation and IGF1 receptor (IGF1R) phosphorylation, wheras the same antibody was found to only partially inhibit the biological activity of the pro-forms. Moreover, we found that the IGF1 pro-form activities can completely be inhibited by neutralising the IGF1R. Finally, we compared the bioactivity of the IGF1 pro-forms to that of mature IGF1, and found that the IGF1 pro-forms were less capable of phosphorylating the IGF1R in the breast cancer-derived cells tested. Our data indicate that IGF1 pro-forms can induce breast cancer cell proliferation via the IGF1R, independent from the mature IGF1 form. These results underline the importance of an accurate assessment of the presence of IGF1 pro-forms within the breast cancer microenvironment.
机构:
Kafrelsheikh Univ, Dept Anat & Embryol, Fac Vet Med, El Geish St, Kafrelsheikh, EgyptKafrelsheikh Univ, Dept Anat & Embryol, Fac Vet Med, El Geish St, Kafrelsheikh, Egypt
El-Magd, Mohammed A.
Saleh, Ayman A.
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机构:
Zagazig Univ, Dept Anim Wealth Dev Vet Genet & Genet Engn, Fac Vet Med, Zagazig, EgyptKafrelsheikh Univ, Dept Anat & Embryol, Fac Vet Med, El Geish St, Kafrelsheikh, Egypt
Saleh, Ayman A.
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机构:
Nafeaa, Abeer A.
El-Komy, Shymaa M.
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h-index: 0
机构:
Tanta Univ, Dept Anim Prod, Fac Agr, Tanta, EgyptKafrelsheikh Univ, Dept Anat & Embryol, Fac Vet Med, El Geish St, Kafrelsheikh, Egypt
El-Komy, Shymaa M.
Afifi, Mohamed A.
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h-index: 0
机构:
Zagazig Univ, Dept Anim Wealth Dev, Biostat, Fac Vet Med, Zagazig, Egypt
Univ Prince Edward Isl, Dept Hlth Management, Atlantic Vet Coll, Charlottetown, PE C1A 4P3, CanadaKafrelsheikh Univ, Dept Anat & Embryol, Fac Vet Med, El Geish St, Kafrelsheikh, Egypt
机构:
Garvan Inst Med Res, Darlinghurst, NSW 2010, Australia
UNSW, Sch Comp Sci & Engn, Sydney, NSW 2052, AustraliaGarvan Inst Med Res, Darlinghurst, NSW 2010, Australia
Ma, David K.G.
Stolte, Christian
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机构:
CSIRO, N Ryde, NSW 1670, AustraliaGarvan Inst Med Res, Darlinghurst, NSW 2010, Australia
Stolte, Christian
Krycer, James R.
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机构:
Univ Sydney, Sch Mol Biosci, Charles Perkins Ctr, Sydney, NSW 2006, AustraliaGarvan Inst Med Res, Darlinghurst, NSW 2010, Australia
Krycer, James R.
James, David E.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Sydney, Sch Mol Biosci, Charles Perkins Ctr, Sydney, NSW 2006, Australia
Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, AustraliaGarvan Inst Med Res, Darlinghurst, NSW 2010, Australia
James, David E.
O'Donoghue, Sean I.
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机构:
Garvan Inst Med Res, Darlinghurst, NSW 2010, Australia
CSIRO, N Ryde, NSW 1670, AustraliaGarvan Inst Med Res, Darlinghurst, NSW 2010, Australia
机构:
Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USALouisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA