Insulin-like growth factor (IGF)-independent action of IGF-binding protein-3 in Hs578T human breast cancer cells. Cell surface binding and growth inhibition

Oh, Youngman; Müller, Hermann L.; Lamson, George; Rosenfeld, Ron G.

doi:10.1016/s0021-9258(18)82426-7

Cited by 419 publications

(21 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to these IGF-dependent actions, IGFBP-3 may have IGF-independent effects via its own cell membrane receptor. The interaction between IGFBP-3 and this receptor results in suppression of cell proliferation (Oh et al, 1993). Finally, IGFBP-3 has been linked to cell growth suppression induced by several anti-proliferative molecules.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Insulin-like growth factor–binding protein-3 and breast cancer survival

Levesque

Khosravi³

et al. 1998

Int. J. Cancer

View full text Add to dashboard Cite

Insulin-like growth factors (IGFs) are potent mitogens involved in the regulation of cell proliferation and apoptosis. The action of IGFs is mediated through a specific cell membrane receptor (IGF-IR), and the interactions between IGFs and this receptor are regulated by IGF-binding proteins (IGFBPs). IGFBP-3 is one such protein which either suppresses or enhances the actions of IGFs. Findings from most in vitro studies suggest that IGFBP-3 inhibits breast cancer cell growth and facilitates apoptosis, but clinical studies have found that high levels of IGFBP-3 in breast cancer tissues are associated with unfavourable prognostic indicators of the disease, such as large tumour size, low levels of steroid hormone receptors, elevated S-phase fraction and DNA aneuploidy. To further examine the role of IGFBP-3 in breast cancer recurrence and survival, we conducted the following nested case-control study. From a cohort of 1,000 women treated surgically for primary breast cancer, we consecutively selected 100 patients who developed recurrent disease after surgery and 100 age-and year of diagnosis-matched patients who had no relapse. Concentrations of IGFBP-3 in breast tissue extracts were determined with an ELISA. Inverse correlations of IGFBP-3 were revealed with estrogen receptor expression and patient age but not with tumour size or S-phase fraction. Levels of IGFBP-3 in breast tissues were slightly higher in the recurrent patients than in controls, but the differences were not statistically significant. No significant association was found between IGFBP-3 and breast cancer recurrence. Survival analysis, however, indicated that the risk of death was increased with higher IGFBP-3 levels, and the association was independent of other prognostic markers. In conclusion, our results demonstrate that high levels of IGFBP-3 are associated with unfavourable prognostic features of breast cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

“…The actions of IGFBP-3 are further regulated by IGFBP proteases, which degrade the binding protein, thereby releasing IGFs from their binding protein (Salahifar et al, 1997). It has also been suggested that IGFBP-3 may have its own cell membrane receptors and exert IGF-independent actions (Oh et al, 1993).…”

mentioning

confidence: 99%

Insulin-like growth factor–binding protein-3 and breast cancer survival

Levesque

Khosravi³

et al. 1998

Int. J. Cancer

View full text Add to dashboard Cite

show abstract

“…12 Accumulating evidence suggests that the IGFBP-3 plays an important role in the regulation of both cell growth and death, independently of its interaction with the IGFs. 13,14 TGF-b is a multifunctional cytokine that belongs to a large family of structurally homologous dimeric proteins. TGF-b exhibits a broad array of biological effects including immunosuppression, regulation of extracellular matrix formation, stimulation of angiogenesis, as well as growth inhibitory or stimulatory effects depending on target cell.…”

mentioning

confidence: 99%

IGF-I and IGFBP-3 augment transforming growth factor-β actions in human renal carcinoma cells

Rosendahl

Forsberg

2006

Kidney International

View full text Add to dashboard Cite

Renal cell carcinoma (RCC) is the most prevalent cancer of the kidney. In human RCC cells, we recently showed that insulin-like growth factor I (IGF-I) has growth-promoting effects regulated by IGF-binding protein 3 (IGFBP-3). In this study, the analysis was expanded to include the interaction between the IGF and transforming growth factor-beta (TGF-beta) systems in the human RCC cells Caki-2 (from a primary tumor) and SK-RC-52 (from a metastasis). Functional effects such as cell proliferation, TGF-beta receptor (TbetaR) signaling, and IGFBP-3 levels were monitored after stimulation with various concentrations of IGF-I, TGF-beta, and IGFBP-3. In addition, human RCC tissues as well as experimental human RCC tumors were analyzed for cellular expression of phosphorylated Smad2 by immunohistochemistry. TGF-beta regulated the endogenous IGFBP-3 levels in these RCC cells as neutralizing anti-TGF-beta(1-3) antibodies strongly reduced the basal IGFBP-3 level. In addition, IGF-I increased the IGFBP-3 levels five- to eightfold with TGF-beta acting in synergy to enhance the IGFBP-3 levels 12- to 17-fold. Neutralizing TGF-beta(1-3) activity circumvented the growth inhibitory effects of IGFBP-3 seen in SK-RC-52, whereas it inhibited the growth-promoting effects of IGFBP-3 in Caki-2. Moreover, IGF-I interacted directly with TGF-beta activation of the TbetaR complex by enhancing phosphorylation and nuclear translocation of Smad2. This study demonstrates a direct interaction of the IGF and TGF-beta systems in human renal carcinoma cells. The observations that IGF-I enhances the TGF-beta signaling and that TGF-beta promotes IGFBP-3 production and thus influence the biological activity of IGF may be of importance for future therapeutic options.

show abstract

“…Because IGFBP-3 can in some instances potentiate IGF activity, our observations of IGFBP-3 in cell membrane-associated and matrix-bound compartments suggest positive effects on endogenous IGF activity throughout intramembraneous bone. Whereas IGFBP-3 may directly activate cells perhaps through its own specific cell surface binding sites [Oh et al, 1993], this has not yet been studied in our culture models. Both cell populations that we examined expressed IGFBP-4 mRNA, but immunoreactive protein was detected only in culture medium (data not shown).…”

Section: Discussionmentioning

confidence: 98%

“…IGFBP-3 appears to be bifunctional, depending upon its association with cellular components, where it is potentiating [Conover 1992, Conover et al, 1996, whether it is in soluble form, where it is inhibitory [DeMellow and Baxter, 1988], or its state of degradation, where proteolysis releases IGF from its complex with IGFBP-3 [Schmid et al, 1991b]. IGFBP-3 also may have IGF-independent actions [Oh et al, 1993]. Cell surface adherence of IGFBP-3 is associated with a lower ligand affinity and in some instances increased biological activity [Jones and Clemmons, 1995].…”

Section: Discussionmentioning

confidence: 99%

Insulin-like growth factor binding proteins localize to discrete cell culture compartments in periosteal and osteoblast cultures from fetal rat bone

Chen

Shu

et al. 1998

J. Cell. Biochem.

View full text Add to dashboard Cite

Insulin-like growth factor (IGF)-I and IGF-II are expressed at biologically effective levels by bone cells. Their stability and activity are modulated by coexpression of IGF binding proteins (IGFBPs). Secreted IGFBPs may partition to soluble, cell-associated, and matrix-bound compartments. Extracellular localization may sequester, store, or present IGFs to appropriate receptors. Of the six IGFBPs known, rat osteoblasts synthesize all but IGFBP-1. Of these, IGFBP-3, -4, and -5 mRNAs are induced by an increase in cAMP. Little is known about extracellular IGFBP localization in bone and nothing about IGFBP expression by nonosteoblastic periosteal bone cells. We compared basal IGFBP expression in periosteal and osteoblast bone cell cultures and assessed the effects of changes in cAMP-dependent protein kinase A or protein kinase C. Basal IGFBP gene expression differed principally in that more IGFBP-2 and -5 occurred in osteoblast cultures, and more IGFBP-3 and -6 occurred in periosteal cultures. An increase in cAMP enhanced IGFBP-3, -4, and -5 mRNAand accordingly increased soluble IGFBP-3, -4, and -5 and matrix-bound IGFBP-3 and -5 in both bone cell populations. In contrast, protein kinase C activators suppressed IGFBP-5 mRNA, and its basal protein levels remained very low. We also detected low Mr bands reactive with antisera to IGFBP-2, -3, and -5, suggesting proteolytic processing or degradation. Our studies reveal that various bone cell populations secrete and bind IGFBPs in selective ways. Importantly, inhibitory IGFBP-4 does not significantly accumulate in cell-associated compartments, even though its secretion is enhanced by cAMP. Because IGFBPs bind IGFs less tightly in cell-bound compartments, they may prolong anabolic effects by agents that increase bone cell cAMP.

show abstract

Insulin-like growth factor (IGF)-independent action of IGF-binding protein-3 in Hs578T human breast cancer cells. Cell surface binding and growth inhibition

Cited by 419 publications

References 68 publications

Insulin-like growth factor–binding protein-3 and breast cancer survival

Insulin-like growth factor–binding protein-3 and breast cancer survival

IGF-I and IGFBP-3 augment transforming growth factor-β actions in human renal carcinoma cells

Insulin-like growth factor binding proteins localize to discrete cell culture compartments in periosteal and osteoblast cultures from fetal rat bone

Contact Info

Product

Resources

About