Involvement of insulin-like growth factor-I and insulin-like growth factor binding proteins in pro-B-cell development

Tomoko Taguchi, Hisami Takenouchi, Jun Matsui, Wei Ran Tang, Mitsuko Itagaki, Yusuke Shiozawa, Kyoko Suzuki, Sachi Sakaguchi, Yohko U. Ktagiri, Takao Takahashi, Hajime Okita, Junichiro Fujimoto, Nobutaka Kiyokawa

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)


Objective. Insulin-like growth factor (IGF)-binding proteins (IGFBPs) are a family of proteins thought to modulate IGF function. By employing an in vitro culture system of human hematopoietic stem cells cocultured with murine bone marrow stromal cells, we examined the effects of IGF-I and IGFBPs on early B-cell development. Materials and Methods. Human CD34+ bone marrow cells were cocultured with murine stromal MS-5 cells for 4 weeks, and pro-B-cell number was analyzed by flow cytometry. After administration of reagents that are supposed to modulate IGF-I or IGFBP function to the culture, the effect on pro-B-cell development was examined. Results. After cultivation for 4 weeks, effective induction of pro-B-cell proliferation was observed. Experiments using several distinct factors, all of which neutralize IGF-I function, revealed that impairment of IGF-I function results in a significant reduction in pro-B-cell development from CD34+ cells. In addition, when the effect of recombinant proteins of IGFBPs and antibodies against IGFBPs were tested, IGFBP-3 was found to inhibit pro-B-cell development, while IGFBP-6 was required for pro-B-cell development. Conclusions. IGF-I is essential for development of bone marrow CD34+ cells into pro-B cells. Moreover, IGFBPs are likely involved in regulation of pro-B-cell development.

Original languageEnglish
Pages (from-to)508-518
Number of pages11
JournalExperimental Hematology
Issue number4
Publication statusPublished - 2006 Apr

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Genetics
  • Cell Biology
  • Cancer Research


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