Inhibition of rat cervical epithelial cell growth by heparin and its reversal by EGF

Wright, Thomas C.; Johnstone, Theresa V.; Castellot, John J.; Karnovsky, Morris J.

doi:10.1002/jcp.1041250320

Cited by 69 publications

(46 citation statements)

References 35 publications

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“…The ability of primary epithelial cells that expressed the 12S protein to be replated could also be due to production of the epithelial cell growth factor(s). Some growth factors bind to the extracellular matrix (6), which modulates the growth responses of epithelial cells (48). We know that this growth factor is found as part of a high-molecular-weight complex (27), which may reflect an interaction with the extracellular matrix.…”

Section: Discussionmentioning

confidence: 99%

Growth factor induction by the adenovirus type 5 E1A 12S protein is required for immortalization of primary epithelial cells.

Quinlan¹,

Whyte²,

Grodzicker³

1988

Mol. Cell. Biol.

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The 12S protein encoded by the adenovirus EIA region induces cellular DNA synthesis in and proliferation and immortalization of primary rat epithelial cells in the presence or absence of serum. It also induces the production of a growth factor(s) that stimulates epithelial cell proliferation. We have undertaken a mutational analysis of the 12S gene to determine the sequences required for these functions. We found that a region near the C-terminus of the 12S protein was required for growth factor induction. No activities have been defined previously for this region. Furthermore, we show that growth factor production was necessary for epithelial cells to survive past their normal life span in culture and to become immortalized. The ability to induce growth factor production required prior expression of EIA activities encoded by the N-terminus of the 12S protein, including activation of quiescent cells into the cell cycle, and an unknown activity that required expression of the first 13 amino acids of the gene. In addition, examination of the subcellular localization of mutant 12S polypeptides suggested new regions that affect the nuclear localization of ElA proteins.

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Section: Discussionmentioning

confidence: 99%

Growth factor induction by the adenovirus type 5 E1A 12S protein is required for immortalization of primary epithelial cells.

Quinlan¹,

Whyte²,

Grodzicker³

1988

Mol. Cell. Biol.

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“…Heparin binds to different cell types and to various plasma proteins, thereby modulating their activity [1][2][3][4]. One could therefore argue that the inhibitory effects of LMWH described above might be attributed to its binding to these cytokines.…”

Section: Lmwh Inhibits Production But Does Not Bind Tnf-amentioning

confidence: 99%

“…Beyond its well understood anticoagulant activity, heparin is known to bind and modulate the activity of various proteins, including cell growth and angiogenic factors [1,2], complement components [3] and adhesion molecules [4]. Heparin also exerts anti-inflammatory activities through interacting with different cell types and modulating their proinflammatory activities by interfering with various processes such as migration and cytokine production [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Inhibitory effects of low molecular weight heparin on mediator release by mast cells: preferential inhibition of cytokine production and mast cell-dependent cutaneous inflammation

Baram

Rashkovsky

Hershkoviz

et al. 1997

Clinical and Experimental Immunology

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SUMMARYThere has been substantial evidence that suggests that heparin may modulate various aspects of immune function and inflammation in addition to its well known anticoagulant activity. In this regard heparin was found to suppress cell-mediated immune responses or asthmatic reactions to allergen challenge. In the present study we analyse the effects of low molecular weight heparin (LMWH) on mast cell degranulation and cytokine production in vitro and on the elicitation of IgE-mediated mast celldependent late cutaneous allergic inflammation in vivo. We have established that LMWH preferentially inhibited tumour necrosis factor-alpha (TNF-a) and IL-4 production without having any significant effect on mast cell degranulation. These effects have been observed in mast cells derived from three different origins that were activated by either immunological or non-immunological stimuli. We have shown that there is inhibition of TNF-a production (and not neutralization of activity), as elimination of the drug after a short preincubation and addition of LMWH to rTNF-a had no effect on TNF-a-mediated cytotoxic activity. These results were also confirmed by ELISA. In vivo, s.c. injection of the LMWH inhibited the leucocyte infiltration associated with the late cutaneous response which followed passive cutaneous anaphylaxis (PCA) reaction, without affecting mast cell numbers or degranulation. These data suggest that LMWH may have an inhibitory role in mast cell-mediated allergic inflammation, and thus might be considered as a possible therapeutic modality.

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“…The 12S induced factor could be bound to high molecular weight carrier proteins, as has been shown for other important mitogens, such as the insulin-like growth factors (31). The components of the extracellular matrix (ECM) modulate the growth responses of epithelial cells (32) and may be important in regulating proliferation in normal and pathologic states. The ECM is composed of high molecular weight proteins and glycosaminoglycans.…”

Section: Mock (+Serum)mentioning

confidence: 99%

Growth factor(s) produced during infection with an adenovirus variant stimulates proliferation of nonestablished epithelial cells.

Quinlan¹,

Sullivan²,

Grodzicker³

1987

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

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Infection of primary baby rat kidney cells with an adenovirus variant that encodes only the 12S gene ofthe ElA region, adenovirus type 5 (Ad5) 12S, results in the production of a growth factor that stimulates primary epithelial cells to proliferate. Increased epithelial cell DNA synthesis and proliferation is detectable between 24 and 36 hr after the addition of conditioned medium from Ad5 12S infected cells and not from cells infected with an ElA deletion mutant virus, Ad5 d1312. This mitogenic factor(s) is effective in the absence of serum and can override the inhibitory effect of serum on primary epithelial cells. Furthermore, there is a requirement for the continued presence of the growth factor(s) in the AdS 12S conditioned medium to maintain epithelial cell proliferation, and the conditioned medium can maintain these cells in a proliferative state for at least 6 wk. The stimulatory activity in AdS 12S conditioned medium is associated with large molecular weight complexes, from which it can be released by 4 M NaCI. Several characteristics of the growth factor(s) indicate that it is a unique mitogen for epithelial cells.The growth of normal animal cells is, in part, controlled by polypeptide growth factors that exert their effect(s) by way of plasma membrane receptor(s) (for review, see ref.

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Inhibition of rat cervical epithelial cell growth by heparin and its reversal by EGF

Cited by 69 publications

References 35 publications

Growth factor induction by the adenovirus type 5 E1A 12S protein is required for immortalization of primary epithelial cells.

Growth factor induction by the adenovirus type 5 E1A 12S protein is required for immortalization of primary epithelial cells.

Inhibitory effects of low molecular weight heparin on mediator release by mast cells: preferential inhibition of cytokine production and mast cell-dependent cutaneous inflammation

Growth factor(s) produced during infection with an adenovirus variant stimulates proliferation of nonestablished epithelial cells.

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