Production of Insulin-Like Growth Factors, Platelet- Derived Growth Factor, and Transforming Growth Factors and Their Role in the Density-Dependent Growth Regulation of a Differentiated Embryonal Carcinoma Cell Line

Zoelen, E.J.J. van; Koornneef, I.; Holthuis, Joost C. M.; Oostwaard, M. J. Wardvan; Feijen, A.; Poorter, T. L. De; Mummery, Christine L.; Buul-Offers, S. C. van

doi:10.1210/endo-124-4-2029

Cited by 24 publications

(9 citation statements)

References 27 publications

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“…Several transformed cell lines produce growth factors such as colony-stimulating factor (G-CSF) [50], fibroblast growth factor (FGF) [51,52], PDGF-like growth factor [53 -55] and insulin-like growth factor I and II (IGF I and IGF II) [53,56,57] via autocrine growth factor loops. These growth factors may be sufficient to drive the cells through different restriction points.…”

Section: G R Cells Stop Cell Cycle Progression At a Point Late In G1mentioning

confidence: 99%

Identification of a restriction point at the M/G1 transition in CHO cells

Hulleman

Bijvelt

Verkleij

et al. 2004

Cellular and Molecular Life Sciences (CMLS)

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The regulation of cell cycle progression in normal mammalian cells is dependent on the presence of growth factors. In their absence, non-transformed cells will stop dividing and enter the quiescent state (G0). We show here that in Chinese hamster ovary cells, at least two serum-dependent points exist during G1 that lead to different cellular responses. The first point is located immediately after mitosis and is suggested to link with apoptosis. The second point is located late in G1, and probably corresponds with the 'classic' restriction point R. Cells depleted of serum after the first restriction point will not stop randomly in G1 but continue G1 progression until they reach the late restriction point, as marked by translocation of p42(MAPkinase) (ERK2) to the nucleus.

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Section: G R Cells Stop Cell Cycle Progression At a Point Late In G1mentioning

confidence: 99%

Identification of a restriction point at the M/G1 transition in CHO cells

Hulleman

Bijvelt

Verkleij

et al. 2004

Cellular and Molecular Life Sciences (CMLS)

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“…Inhibition was expressed as a percentage relative to control cultures in the absence of TGFβ. EPI-7 cells were used as a control for the TGFβ inhibition assay [50].…”

Section: Dna Synthesismentioning

confidence: 99%

Mouse embryonic stem cells with aberrant transforming growth factor β signalling exhibit impaired differentiation in vitro and in vivo

et al. 1998

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“…However, when the cell-secreted factors are unknown, one is typically limited to varying cell density and looking for density-dependent phenotypes. Because autocrine loops can be self-sufficient even at clonal density (6), these methods are incomplete.…”

mentioning

confidence: 99%

Attenuation of extrinsic signaling reveals the importance of matrix remodeling on maintenance of embryonic stem cell self-renewal

Przybyla¹,

Voldman

2012

Proc. Natl. Acad. Sci. U.S.A.

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The role of extrinsic factors in maintaining self-renewal of embryonic stem cells (ESCs) has been extensively studied since the cells' isolation, but the necessity for cell-secreted factors in self-renewal has remained undefined to date. Although it is generally accepted that addition of leukemia inhibitory factor (LIF) together with either serum or bone morphogenetic protein 4 (BMP4) is sufficient to maintain mouse ESCs (mESCs) in a selfrenewing state, this does not preclude the possibility that autocrine factors are also required. Here we make use of a microfluidic perfusion device that is able to globally diminish diffusible autocrine signaling by applying continuous media flow to deplete cellsecreted factors. We demonstrate mESC culture for several days under continuous microfluidic perfusion and show that cell-secreted factors are removed and can be recovered downstream. We find that perturbing cell-secreted signaling causes mESCs to exit their stable self-renewing state in defined conditions that normally support self-renewal and to exhibit properties characteristic of epiblast cells. This state change is not due to the presence of the known autocrine differentiation inducer fibroblast growth factor 4, but, remarkably, it can be prevented by global remodeling of the extracellular matrix (ECM). We also find that cell-secreted matrix remodeling proteins are removed under perfusion and that inhibition of extracellular matrix remodeling causes mESCs to differentiate. Taken together, our data indicate that LIF and BMP4 are not sufficient to maintain self-renewal and that cell-secreted factors are necessary to continuously remodel the ECM and thereby prevent differentiation, revealing a previously undescribed level of mESC regulation through the use of microfluidic perfusion technology. I t has long been known that cell-secreted signals are required for cellular processes such as growth, survival, differentiation, metastasis, and apoptosis (1-5). However, the precise contributions of autocrine and/or paracrine signals to a particular process are often difficult to determine. When the cell-secreted factors and/or receptors are known, one can use chemical or genetic inhibition of target molecules, derivation of knockout cell lines, or overexpression of candidate molecules and receptors to study autocrine/paracrine processes. However, when the cell-secreted factors are unknown, one is typically limited to varying cell density and looking for density-dependent phenotypes. Because autocrine loops can be self-sufficient even at clonal density (6), these methods are incomplete.Pluripotent stem cells isolated from the developing blastocyst are well-suited for the study of cell-secreted signaling, because extrinsic signals generated by the embryo are essential for proper development (7,8), and autocrine and paracrine signals are likewise important in stem cell self-renewal (9), growth (3), and differentiation (1, 10). Mouse embryonic stem cells (mESCs) are pluripotent cells derived from the inner cell mass of preimplanta...

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Production of Insulin-Like Growth Factors, Platelet- Derived Growth Factor, and Transforming Growth Factors and Their Role in the Density-Dependent Growth Regulation of a Differentiated Embryonal Carcinoma Cell Line

Cited by 24 publications

References 27 publications

Identification of a restriction point at the M/G1 transition in CHO cells

Identification of a restriction point at the M/G1 transition in CHO cells

Mouse embryonic stem cells with aberrant transforming growth factor β signalling exhibit impaired differentiation in vitro and in vivo

Attenuation of extrinsic signaling reveals the importance of matrix remodeling on maintenance of embryonic stem cell self-renewal

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