An Interaction between Insulin-like Growth Factor-binding Protein 2 (IGFBP2) and Integrin α5 Is Essential for IGFBP2-induced Cell Mobility

Wang, George K.; Hu, Limei; Fuller, Gregory N.; Zhang, Wei

doi:10.1074/jbc.m513686200

Cited by 110 publications

(105 citation statements)

References 24 publications

(24 reference statements)

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“…In addition, we observed that IGFBP2 alone has no effect on astrocytoma cell growth in vitro, whereas it positively affects astrocytoma cell motility. Both results are in agreement with previous studies recently published in literature (Levitt et al, 2005;Wang et al, 2003Wang et al, , 2006. The latter of these studies reported that IGFBP2 promotes astrocytoma cell motility through interaction between the integrin a5 subunit and its RGD domain.…”

Section: Discussionsupporting

confidence: 93%

“…The data are expressed in terms of means 6 SE normalized so that the control (CT) mean was set to 100. As compared with CT, only the significant differences (posthoc tests) are indicated as *P < 0.05, **P < 0.01, and ***P < 0.001. the IGFBP2-IGFII complex may also prevent the interaction between the IGFBP2 RGD domain and the integrin a5 subunit, showed by Wang et al (2006) as being essential for the IGFBP2-induced cell motility.…”

Section: Discussionmentioning

confidence: 99%

“…Although IGFBP2 was classically considered as a growth inhibitor, its overexpression is observed in high-grade astrocytomas as compared with low-grade astrocytomas and associated with poor patient survival (Rorive et al, 2006;Sallinen et al, 2000). Actually, IGF-independent effects of IGFBP2 have been described (Hoeflich et al, 2001), and recently, Wang et al (2006) showed that IGFBP2 positively modulates astrocytoma cell migration through interaction between its Arg-Gly-Asp (RGD) domain and the integrin a5 subunit.…”

Section: Introductionmentioning

confidence: 99%

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Matrix metalloproteinase‐9 interplays with the IGFBP2–IGFII complex to promote cell growth and motility in astrocytomas

Rorive

Berton

D’Haene

et al. 2008

Glia

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Insulin-like growth factor II (IGFII) acts as a potent mitogen for several tumor types and has been reported to positively influence astrocytoma cell growth and motility. In the central nervous system, IGFII bioavailability is mainly modulated by insulin-like growth factor binding protein 2 (IGFBP2), which sequestrates IGFII and therefore prevents its interaction with the type-1 IGF receptor (IGF-IR). Proteolysis of IGFBP2 is the predominant mechanism recognized to reduce the binding affinity of IGFBP2 for IGFII, thus favoring dissociation of IGFII from the IGFBP2-IGFII complex. It is known that certain proteases involved in astrocytoma malignancy, such as matrix metalloproteinase-7 (MMP-7), plasmin, and cathepsin D, are able to proteolyze IGFBP2 in vitro. The present study aims to investigate whether other proteases expressed by astrocytomas, specifically MMP-2, MMP-9, and membrane-type 1 matrix metalloprotease (MT1-MMP), are able to proteolyze the IGFBP2-IGFII complex. Our results show the following: (i) MMP-9 proteolyzes the IGFBP2-IGFII complex in vitro, while MMP-2 and MT1-MMP do not; (ii) this MMP-9-induced IGFBP2-IGFII complex proteolysis releases free IGFII, which contributes to enhance the motility and the growth of LN229 astrocytoma cells. Furthermore, this study also highlights that the formation of the IGFBP2-IGFII complex inhibits IGFBP2's cell motility promoting effect by reducing the pool of free IGFBP2. In conclusion, MMP-9-induced IGFBP2 proteolysis may be regarded as an important post-translational event involved in astrocytoma aggressiveness. These new findings support drug targeting of MMP-9 as an interesting approach in the treatment of astrocytoma. V V C

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Matrix metalloproteinase‐9 interplays with the IGFBP2–IGFII complex to promote cell growth and motility in astrocytomas

Rorive

Berton

D’Haene

et al. 2008

Glia

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“…Recent data support this hypothesis, in that IGFBP2 was shown to independently promote cell mobility through its interaction with integrins (Schütt et al, 2004;Wang et al, 2006). Moreover, IGFBP2 has been described to be a candidate biomarker for PTEN status and PI3K/Akt pathway activation (Mehrian-Shai et al, 2007).…”

Section: Discussionmentioning

confidence: 51%

Activity of the multikinase inhibitor dasatinib against ovarian cancer cells

Glas

Dering

et al. 2009

Br J Cancer

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BACKGROUND: Here, we explore the therapeutic potential of dasatinib, a small-molecule inhibitor that targets multiple cytosolic and membrane-bound tyrosine kinases, including members of the Src kinase family, EphA2, and focal adhesion kinase for the treatment of ovarian cancer. METHODS: We examined the effects of dasatinib on proliferation, invasion, apoptosis, cell-cycle arrest, and kinase activity using a panel of 34 established human ovarian cancer cell lines. Molecular markers for response prediction were studied using gene expression profiling. Multiple drug effect/combination index (CI) isobologram analysis was used to study the interactions with chemotherapeutic drugs. RESULTS: Concentration-dependent anti-proliferative effects of dasatinib were seen in all ovarian cancer cell lines tested, but varied significantly between individual cell lines with up to a 3 log-fold difference in the IC 50 values (IC 50 range: 0.001 -11.3 mmol l À1 ). Dasatinib significantly inhibited invasion, and induced cell apoptosis, but less cell-cycle arrest. At a wide range of clinically achievable drug concentrations, additive and synergistic interactions were observed for dasatinib plus carboplatin (mean CI values, range: 0.73 -1.11) or paclitaxel (mean CI values, range: 0.76 -1.05). In this study, 24 out of 34 (71%) representative ovarian cancer cell lines were highly sensitive to dasatinib, compared with only 8 out of 39 (21%) representative breast cancer cell lines previously reported. Cell lines with high expression of Yes, Lyn, Eph2A, caveolin-1 and 2, moesin, annexin-1, and uPA were particularly sensitive to dasatinib. CONCLUSIONS: These data provide a clear biological rationale to test dasatinib as a single agent or in combination with chemotherapy in patients with ovarian cancer.

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“…While IGFBP2 exhibits IGF-dependent inhibitory effects on growth of many types of cells [137], it also displays IGF-independent activities [69,70,[138][139][140][141][142][143][144][145][146]. We identified IGFBP2 from a cancerous cell line as a supportive secreted factor for mouse and human HSCs [69,147].…”

Section: Igf Binding Proteinmentioning

confidence: 99%

Ex vivo expansion of hematopoietic stem cells

Xie

Zhang

2015

Sci. China Life Sci.

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Ex vivo expansion of hematopoietic stem cells (HSCs) would benefit clinical applications in several aspects, to improve patient survival, utilize cord blood stem cells for adult applications, and selectively propagate stem cell populations after genetic manipulation. In this review we summarize and discuss recent advances in the culture systems of mouse and human HSCs, which include stroma/HSC co-culture, continuous perfusion and fed-batch cultures, and those supplemented with extrinsic ligands, membrane transportable transcription factors, complement components, protein modification enzymes, metabolites, or small molecule chemicals. Some of the expansion systems have been tested in clinical trials. The optimal condition for ex vivo expansion of the primitive and functional human HSCs is still under development. An improved understanding of the mechanisms for HSC cell fate determination and the HSC culture characteristics will guide development of new strategies to overcome difficulties. In the future, development of a combination treatment regimen with agents that enhance self-renewal, block differentiation, and improve homing will be critical. Methods to enhance yields and lower cost during collection and processing should be employed. The employment of an efficient system for ex vivo expansion of HSCs will facilitate the further development of novel strategies for cell and gene therapies including genome editing. ex vivo expansion, hematopoietic stem cells, niche, signal transduction, cord blood, transplantation, SCID-repopulating cell, genome editing, CRISPR/Cas9 Citation:Xie JJ, Zhang CC. Ex vivo expansion of hematopoietic stem cells.

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An Interaction between Insulin-like Growth Factor-binding Protein 2 (IGFBP2) and Integrin α5 Is Essential for IGFBP2-induced Cell Mobility

Cited by 110 publications

References 24 publications

Matrix metalloproteinase‐9 interplays with the IGFBP2–IGFII complex to promote cell growth and motility in astrocytomas

Matrix metalloproteinase‐9 interplays with the IGFBP2–IGFII complex to promote cell growth and motility in astrocytomas

Activity of the multikinase inhibitor dasatinib against ovarian cancer cells

Ex vivo expansion of hematopoietic stem cells

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