Insulin-like growth factors I and II are present in the skeletal tissues of ten vertebrates

Bautista, Catalino M.; Mohan, Subburaman; Baylink, David J.

doi:10.1016/0026-0495(90)90154-5

Cited by 119 publications

(41 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this way, stimulatory effects of IGF-II may reflect ability to regulate IGFBP-4, independent of IGF-II cross-reactivity with the type I IGF receptor. This mechanism could play a significant role in bone with its high concentration of IGF-II in bone matrix (47), osteoblastic production of IGFBP-4 (7,25), and IGF-regulated IGFBP-4 protease activity (25 and unpublished results). On the other hand, if intact IGFBP-4 is an important inhibitor of IGF-I-stimulated growth, then cell types which secrete IGFBP-4 but block localized IGFBP-4 proteolysis (via inhibitors of proteolysis and/or decreased IGFBP-4 protease production) would be expected to have limited responsiveness to IGFs.…”

Section: Discussionmentioning

confidence: 94%

Posttranslational regulation of insulin-like growth factor binding protein-4 in normal and transformed human fibroblasts. Insulin-like growth factor dependence and biological studies.

Conover¹,

Kiefer²,

Zapf³

1993

J. Clin. Invest.

170

View full text Add to dashboard Cite

Insulin-like growth factor binding protein4 (IGFBP4) is a 24-26-kD protein expressed by a variety of cell types in vivo and in vitro. Treatment of normal adult human fibroblasts with 10 nM insulin-like growth factor II (IGF-II) for 24 h resulted in an 85% decrease in endogenous IGFBP4, as assessed by Western ligand blot analysis of the conditioned medium. Incubation of human fibroblast-conditioned medium (HFCM) with IGF-II under cell-free conditions led to a similar loss of IGFBP4. This posttranslationally regulated decrease in IGFBP-4 appeared to be due to a protease in HFCM: (a) It could be prevented with specific protease inhibitors or incubation at 40C; (b) proteolysis of recombinant human (rh) IGFBP-4 required HFCM; (c) immunoblotting and radiolabeling confirmed cleavage of IGFBP4 into 18-and 14-kD IGFBP4 fragments. The protease was specific for IGFBP4, and was strictly dependent on IGFs for activation. IGF-II was the most effective of the natural and mutant IGFs tested, inducing complete hydrolysis of rhIGFBP4 at a molar ratio of 0.25:1 (IGF/IGFBP4). Simian virus 40-transformed adult human fibroblasts also expressed IGFBP4 and IGFBP4 protease, as well as an inhibitor of IGFBP4 proteolysis. In biological studies, intact rhIGFBP4 potently inhibited IGF-I-stimulated [3HIaminoisobutyric acid uptake, whereas proteolyzed rhIGFBP-4 had no inhibitory effect. In conclusion, these data provide evidence for a novel IGF-dependent IGFBP4-specific protease that modifies IGFBP4 structure and function, and indicate a preferential role for IGF-II in its activation. Posttranslational regulation of IGFBP4 may provide a means for cooperative control of local cell growth by IGF-I and IGF-II.

show abstract

Section: Discussionmentioning

confidence: 94%

Posttranslational regulation of insulin-like growth factor binding protein-4 in normal and transformed human fibroblasts. Insulin-like growth factor dependence and biological studies.

Conover¹,

Kiefer²,

Zapf³

1993

J. Clin. Invest.

170

View full text Add to dashboard Cite

show abstract

“…Bone has been shown to be a major source of IGFs with humans having the highest concentration of total somatomedins (38). Studies have shown that human prostate and ovarian cancer cell lines grow by an autocrine loop in which IGF-I activates its receptor and interference with activation of the receptor leads to cessation of growth in vitro (39,40).…”

Section: Methodsmentioning

confidence: 99%

Antisense RNA to the type I insulin-like growth factor receptor suppresses tumor growth and prevents invasion by rat prostate cancer cells in vivo.

Burfeind

Chernicky²,

Rininsland³

et al. 1996

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

214

141

View full text Add to dashboard Cite

Prostate carcinoma is the second leading cause of death from malignancy in men in the United States. Prostate cancer cells express type I insulin-like growth factor receptor (IGF-IR) and prostate cancer selectively metastazises to bone, which is an environment rich in insulin-like growth factors (IGFs), thereby supporting a paracrine action for cancer cell proliferation. We asked whether the IGF-IR is coupled to tumorigenicity and invasion of prostate cancer. When rat prostate adenocarcinoma cells (PA-III) were stably transfected with an antisense IGF-IR expression construct containing the ZnSO4-inducible metallothionein-1 transcriptional promoter, the transfectants expressed high levels of IGF-IR antisense RNA after induction with ZnSO4, which resulted in dramatically reduced levels of endogenous IGF-IR mRNA. A significant reduction in expression both of tissuetype plasminogen activator and of urokinase-type plasminogen activator occurred in PA-III cells accompanying inhibition of IGF-IR. Prostate carcinoma is the most commonly diagnosed cancer in men and the second leading cause of death from malignancy in men in the United States (1). If diagnosed after the carcinoma metastazises, prostatic cancer is a fatal disease for which there is no cure (2). Prostate cancer preferentially metastazises to bone where insulin-like growth factors (IGFs) are two of the most abundant growth factors (3). Prostate cancer cells express type I insulin-like growth factor receptor (IGF-IR), which could faciliate the development of bone metastases because IGFs are required for cell growth.The IGF-IR has been shown to play a central role in the mechanism of transformation (4). Human prostate cancer cells have been shown to express binding sites for insulin-like growth factor I (IGF-I) (5). Receptor studies have demonstrated the presence of specific binding sites for IGF-I on rat prostate adenocarcinoma cells (PA-III) (6). These cells were obtained from a spontaneously occurring tumor in an aged Lobund-Wistar (L-W) rat (7). The Pollard system of transplantable prostate tumors has been demonstrated to be an extremely useful model for the evaluation of antimetastatic and cytotoxic agents for the treatment of androgen-insensitive prostatic cancer (8,9). Moreover, a recent study strongly supports the validity of the Pollard model of spontaneous prostate cancer in L-W rats (10). Therefore, we have applied our antisense strategy using an IGF-IR construct to study the effect of blocking the IGF-IR on tumorgenesis of transfected PA-III cells in vivo.We have reported that treatment of rat glioblastoma (11) and mouse teratocarcinoma (12) with our antisense constructs to IGF-I resulted in complete regression of tumors in syngeneic animals. Furthermore, an identical antitumorigenic effect has been described for C6 glioblastoma cells that were treated with a similar antisense RNA strategy that targeted the IGF-IR (13). In this study, we demonstrate that the L-W rat prostate cancer cells, PA-III, express the IGF-IR; however, we could not de...

show abstract

“…Breast cancer cells may prefer bone to other organs because of the growth factors in the microenvironment. Bone has been shown to be a major source of IGFs, with humans having the highest concentration of total skeletal somatomedins of all species studies (Bautista et al, 1990). Indeed, IGF-II is the most abundant growth factor stored in bone matrix.…”

Section: Abstract /Maximum 1öö " ■mentioning

confidence: 99%

Episome-Based Gene Therapy Strategy for Treatment of Human Breast Cancer

Ilan¹

1999

View full text Add to dashboard Cite

Insulin-like growth factors I and II are present in the skeletal tissues of ten vertebrates

Cited by 119 publications

References 29 publications

Posttranslational regulation of insulin-like growth factor binding protein-4 in normal and transformed human fibroblasts. Insulin-like growth factor dependence and biological studies.

Posttranslational regulation of insulin-like growth factor binding protein-4 in normal and transformed human fibroblasts. Insulin-like growth factor dependence and biological studies.

Antisense RNA to the type I insulin-like growth factor receptor suppresses tumor growth and prevents invasion by rat prostate cancer cells in vivo.

Episome-Based Gene Therapy Strategy for Treatment of Human Breast Cancer

Contact Info

Product

Resources

About