Transforming growth factor β and platelet-derived growth factor in human myometrium and in uterine leiomyomas at various stages of tumour growth

Wolańska, Małgorzata; Bańkowski, Edward

doi:10.1016/j.ejogrb.2006.01.034

Cited by 19 publications

(25 citation statements)

References 23 publications

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“…We demonstrated that fibroids within the same woman often have different growth rates despite having a similar hormonal milieu. Indeed, each tumor appeared to have its own intrinsic growth rate, consistent with studies showing that fibroids are monoclonal in origin (15,16) with variable molecular characteristics (17)(18)(19)(20)(21). The only other large study of fibroid growth was conducted in Japan, and most of the 70 participants had only a single tumor (11); thus, variation in growth of fibroids from the same woman could not be evaluated.…”

Section: Discussionsupporting

confidence: 54%

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Growth of uterine leiomyomata among premenopausal black and white women

Peddada

Laughlin

Miner

et al. 2008

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

307

227

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Uterine leiomyomata (fibroids) are the leading cause of hysterectomy in the United States. Black women have a greater fibroid burden than whites, yet no study has systematically evaluated the growth of fibroids in blacks and whites. We prospectively tracked growth for 262 fibroids (size range: 1-13 cm in diameter) from 72 premenopausal participants (38 blacks and 34 whites). Fibroid volume was measured by computerized analysis of up to four MRI scans over 12 months. We used mixed effects models to identify factors that are associated with growth, and results were converted to percent change per 6 months for clinical relevance. The median growth rate was 9% (range: ؊89% to ؉138%). Seven percent of fibroids regressed (>20% shrinkage). Tumors from the same woman grew at different rates (within-woman component of variation was twice the component among women; both were significant, P < 0.001). Black and white women less than 35 years of age had similar fibroid growth rates. However, growth rates declined with age for whites but not for blacks (P ‫؍‬ 0.05). The odds of a tumor growing more than 20% in 6 months also decreased with age for whites but not for blacks (P < 0.01). Growth rates were not influenced by tumor size, location, body mass index, or parity. We conclude that (i) spontaneous regression of fibroids occurs; (ii) fibroids from the same woman grow at different rates, despite a uniform hormonal milieu; (iii) fibroid size does not predict growth rate; and (iv) age-related differences in fibroid growth between blacks and whites may contribute to the higher symptom burden for black women.ethnic ͉ fibroid ͉ MRI ͉ tumor growth ͉ longitudinal data U terine leiomyomata (fibroids) are the leading indication for hysterectomy in the United States (1). Myomectomy and uterine artery embolization are also common treatments, but hysterectomy may be required subsequently (2). Hartmann et al. (3) estimate a $4,600 excess health care cost during the year following each US woman's diagnosis of fibroids. National medical costs associated with fibroids exceed 2 billion dollars annually (4). African Americans have a higher fibroid incidence (5, 6), experience more severe symptoms (7), present with larger tumors (7), and have a threefold higher risk of hysterectomy (8) compared with whites. Symptoms increase with the size of fibroids (7, 9, 10). However, few studies have examined the growth of fibroids over time (11-13), and no study has systematically followed the growth of fibroids in black and white women.The Fibroid Growth Study was designed to measure the growth of fibroids in black and white women with clinically relevant fibroids using MRI technology. We compare growth rates of individual tumors from the same woman; contrast fibroid growth in black and white women; and examine associations with age, parity, body mass index (BMI), and tumor characteristics. ResultsStudy Participants. Characteristics of the 72 participants are shown in Table 1. Our cohort ranged in age from 24 to 54 years, and approximately half were Afri...

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Section: Discussionsupporting

confidence: 54%

“…Tumor size has been related to variation in molecular markers (17,(19)(20)(21), and it has been assumed that the molecular differences reflect differences in tumor growth rates. Our data show that large tumor size cannot be used as an indicator of a growing tumor.…”

Section: Discussionmentioning

confidence: 99%

Growth of uterine leiomyomata among premenopausal black and white women

Peddada

Laughlin

Miner

et al. 2008

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

307

227

View full text Add to dashboard Cite

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“…However, it appears that PDGF does not act alone, but acts in concert with other growth factors such as TGF-β, EGF, and the IGFs. For example, low amounts of TGF-β stimulate autocrine PDGF secretion and promotes the synthesis of PDGF receptors (28). When myometrial cells are treated with both PDGF and EGF, there is a synergistic decrease in DNA synthesis, whereas treatment of leiomyoma cells with both factors results in an additive increase in DNA synthesis (26).…”

Section: Discussionmentioning

confidence: 99%

Differential Expression of Receptor Tyrosine Kinases (RTKs) and IGF-I Pathway Activation in Human Uterine Leiomyomas

Saile

Swartz

et al. 2008

Mol Med

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Uterine leiomyomas (fibroids) are benign tumors that are prevalent in women of reproductive age. Research suggests that activated receptor tyrosine kinases (RTKs) play an important role in the enhanced proliferation observed in fibroids. In this study, a phospho-RTK array technique was used to detect RTK activity in leiomyomas compared with myometrial tissue. We found that fifteen out of seventeen RTKs evaluated in this study were highly expressed (P < 0.02-0.03) in the leiomyomas, and included the IGF-I/IGF-IR, EGF/EGFR, FGF/FGF-R, HGF/HGF-R, and PDGF/PDGF-R gene families. Due to the higher protein levels of IGF-IR observed in leiomyomas by us in earlier studies, we decided to focus on the activation of the IGF-IR, its downstream effectors, and MAPKp44/42 to confirm our earlier findings; and validate the significance of the increased IGF-IR phosphorylation observed by RTK array analysis in this study. We used immunolocalization, western blot, or immunoprecipitation studies and confirmed that leiomyomas overexpressed IGF-IRβ and phosphorylated IGF-IRβ. Additionally, we showed that the downstream effectors, Shc, Grb2, and MAPKp44/42 (P < 0.02-0.001) were also overexpressed and involved in IGF-IR signaling in these tumors, while IRS-I, PI3K, and AKT were not. In vitro studies showed that IGF-I (100 ng/mL) increased the proliferation of uterine leiomyoma cells (UtLM) (P < 0.0001), and that phosphorylated IGF-IRβ, Shc, and MAPKp44/42 were also overexpressed in IGF-I-treated UtLM cells (P < 0.05), similar to the tissue findings. A neutralizing antibody against the IGF-IRβ blocked these effects. These data indicate that overexpression of RTKs and, in particular, activation of the IGF-IR signaling pathway through Shc/Grb2/MAPK are important in mediating uterine leiomyoma growth. These data may provide new anti-tumor targets for noninvasive treatment of fibroids.

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“…Studies have shown that PDGF, TNF-a, and IL-1b induce the secretion of precursor and/or mature forms of the enzyme from cultured fibroblasts [5,22]. The expressions of these factors are higher in large leiomyomas when compared with small tumours [23][24][25]. Thus, they may be responsible for CATB up-regulation during myoma growth.…”

Section: Commentmentioning

confidence: 99%