Cited by 115Multiple Myeloma Research and TreatmentsGrowth Hormone and Insulin-like Growth FactorsPI3K/AKT/mTOR signaling in cancer

Specific roles for the PI3K and the MEK-ERK pathway in IGF-1-stimulated chemotaxis, VEGF secretion and proliferation of multiple myeloma cells: study in the 5T33MM model

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Menu, E, Kooijman, R, Valckenborgh, E Van, Asosingh, K, Bakkus, M, Camp, B Van, Vanderkerken, K·2004·British Journal of Cancer

Abstract

Insulin-like growth factor-1 (IGF-1) has been described as an important factor in proliferation, cell survival and migration of multiple myeloma (MM) cells. Angiogenesis correlates with development and prognosis of the MM disease. Vascular endothelial growth factor (VEGF) is one of the prominent factors involved in this process. The different functions of IGF-1 were investigated in the 5TMM mouse model with emphasis on proliferation, migration and VEGF secretion, and the signalling pathways involved. Western Blot analysis revealed that ERK1/2 and Akt (PKB) were activated after IGF-1 stimulation. The activation of ERK1/2 was reduced by the PI3K inhibitor Wortmannin, implying that the PI3K pathway is involved in its activation. Insulin-like growth factor-1 induced an increase in DNA synthesis in MM cells, which was mediated by a PI3K/Akt-MEK/ERK pathway. Insulin-like growth factor-1 enhanced F-actin assembly and this process was only PI3K mediated. Stimulation by IGF-1 of VEGF production was reduced by PD98059, indicating that only the MEK-ERK pathway is involved in IGF-1-stimulated VEGF production. In conclusion, IGF-1 mediates its multiple effects on MM cells through different signal transduction pathways. In the future, we can study the potential in vivo effects of IGF-1 inhibition on tumour growth and angiogenesis in MM.

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  • IGF1 and IGF2 bind IGF1R, which elicits phosphorylation of intracellular adaptor proteins and activation of MAPK and PI3K/AKT signaling pathways.

    “The two main IGFs, IGF1 and IGF2, bind the IGF1 receptor (IGF1R), which elicits phosphorylation of intracellular adaptor proteins and activation of MAPK and PI3K/AKT signaling pathways [223].”

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Authors
Menu, E., Kooijman, R., Valckenborgh, E. V., Asosingh, K., Bakkus, M., Camp, B. V., & Vanderkerken, K.
Affiliations
Vrije Universiteit Brussel (BE)
Corresponding author
Vanderkerken, K
Venue
British Journal of Cancer
Published
2004-03
Volume
90
Issue
5
Pages
1076-1083
ISSN
  • 0007-0920 (ISSN-L)
  • 1532-1827
OpenAlex
W2049101520
Cited by
115
References
49
Citations by year
2026: 3 · 2025: 3 · 2024: 4 · 2023: 5 · 2022: 3 · 2021: 3 · 2020: 7 · 2019: 4 · 2018: 4 · 2017: 1 · 2016: 3 · 2015: 4 · 2014: 5 · 2013: 8 · 2012: 3
FWCI
6.92
Type
journal article
Language
en
Open access
Locations
  • British Journal of Cancer (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • VUBIR (Vrije Universiteit Brussel) (submittedVersion)
Funders
  • Fonds Wetenschappelijk Onderzoek
  • Vrije Universiteit Brussel
  • Vlaamse regering
Topics
  • Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Keywords
insulin-like growth factor I, multiple myeloma, PI3K/Akt signaling, MEK/ERK signaling, VEGF secretion, cell proliferation, cell migration, angiogenesis, F-actin assembly, wortmannin, PD98059, ERK1/2 activation
MeSH terms
Animals, Cell Division, Cell Movement, Chemotaxis, Disease Models, Animal, Flavonoids, Humans, Insulin-Like Growth Factor I, Mice, Inbred C57BL, Multiple Myeloma, Neovascularization, Pathologic, Phosphorylation, Proto-Oncogene Proteins, Tumor Cells, Cultured, Signal Transduction, Down-Regulation, Protein Serine-Threonine Kinases, Phosphatidylinositol 3-Kinases, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinases, Mitogen-Activated Protein Kinase Kinases, Vascular Endothelial Growth Factor A, Mitogen-Activated Protein Kinase 3, Proto-Oncogene Proteins c-akt, Mice

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