Peptide growth factors and the adrenal cortex

Increasing evidence suggests that the actions of classical stimulants of adrenocortical growth and function, such as ACTH or dietary sodium restriction, may partially be mediated via locally produced regulators. Several peptide growth factors, such as basic fibroblast growth factor, insulin-like growth factors, and transforming growth factor-beta 1, have emerged in recent years as multifunctional molecules that typically play such regulatory roles. Adrenocortical cells are highly responsive to these growth factors, in particular in the regulation of cell growth and differentiated functions, such as steroidogenesis. In addition, growth factor expression in the adrenal cortex has been shown to be regulated by physiological stimulants. The spatial expression, release, and activation of these growth factors may, therefore, locally mediate or amplify the actions of the hypothalamo-pituitary axis and the renin-angiotensin system on adrenocortical proliferation, differentiation, and steroidogenesis.     

Peptide growth factors in normal and hypertrophied bladder

The pharmacokinetics of oral zidovudine in HIV-infected children and adults are reported. Fourty-six patients were investigated. For data analysis three groups of similar size were formed: young children 4 months-4 years, n = 15 (group 1), older children up to 13 years, n = 16 (group 2) and young adults, n = 15 (group 3). After a single oral dose repeated blood samples were taken 1/2 hourly during a period of 4 hours and zidovudine concentrations in plasma were determined by high performance liquid chromatography. For better comparison of dose dependent parameters peak concentrations (Cmax) and the area under the time-concentration curves (AUC) were normalized either to the dose/body weight (bw) or the dose/body surface area (bs), respectively. Time to reach peak concentrations and mean terminal elimination half-life times (t1/2 beta = 63.4 +/- 47.6, 74.9 +/- 54.9 and 56.9 +/- 16.4 min in group 1, 2 and 3, respectively, mean +/- SD) were not significantly different between the three groups. With normalization to dose/bw young children in comparison to adults had significantly lower Cmax (2.7 +/- 1.3 vs. 4.6 +/- 2.4 mumol/l, p = 0.016) and AUC (226 +/- 108 vs. 373 +/- 224 mumol.min/l, p = 0.038). Group 2 gave intermediate values. However, with normalization to dose/bs differences in Cmax (6.5 +/- 3.3, 7.3 +/- 4.2 and 6.8 +/- 3.6 mumol/l, in group 1, 2, and 3, respectively) and AUC (563 +/- 313, 691 +/- 351 and 555 +/- 342 mumol.min/l, in group 1, 2 and 3) were not significant between the three groups. It is likely that changes in body water content with age may account for most of these differences observed. In conclusion, a similar pharmacokinetic profile was found in children older than 3 months as compared to older children or adults.     

Regulation of prostate growth by fibroblast growth factors

Growth of the prostate is controlled by androgen. However, there is information indicating that androgen may not act directly, but may act indirectly through polypeptide growth factors, to control prostate growth. This review will focus on the involvement of members of the fibroblast growth factor (FGF) family in this process. The properties of FGFs and FGF-receptors are described that implicate these molecules in growth control. Information is provided that prostate stromal cells synthesize FGF2 and FGF7. FGF2 is a potent mitogen for stromal cells; whereas, FGF7 is exclusively a mitogen for epithelial cells. Transforming growth factor beta (TGF beta), also produced by prostate cells, inhibit cell growth. This suggests that prostate growth is controlled by autocrine and paracrine mechanisms. Evidence is presented that altered FGF expression accompanies benign prostatic hyperplasia and prostate cancer. A model is proposed whereby androgen regulates TGF beta, influencing FGF2 and FGF7 expression, and in turn regulating growth of the prostatic stroma and epithelium. An imbalance in the influence of these growth factors may contribute to prostate disease.     

Psychosocial factors as mediators of acupuncture therapy.

Investigated a number a psychosocial variables that have been suggested as possible mediating factors in acupuncture therapy. 42 patients (mean age 46.7 yrs) with bursitis and/or tendonitis of the shoulder served as Ss. All were randomly assigned to 1 of 4 treatment groups: acupuncture-positive milieu, acupuncture-negative milieu, placebo acupuncture-positive milieu, and placebo acupuncture-negative milieu. Pretreatment and posttreatment subjective pain reports and shoulder motion studies, as well as pretreatment assessments of hypnotic susceptibility and suggestibility, were determined for each S. Results indicate that (a) acupuncture and placebo acupuncture were equally effective in producing highly significant reductions in subjective pain reports; (c) Ss treated in the positive milieu reported more improvement than those in the negative milieu; and (d) hypnotic susceptibility, suggestibility, belief in the treatment, and the satisfaction of expectations showed no relationship to treatment outcome. It is concluded that acupuncture therapy provides a powerful placebo. Treatment milieu variables warrant future study in the attempt to understand the acupuncture phenomena. (22 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Peptide growth factors: clinical and therapeutic strategies

Total internal reflection fluorescence microscopy has been used to investigate the binding of the soluble extracellular domain of mouse Fc gamma RII (sFc gamma RII) to an anti-trinitrophenyl monoclonal mouse IgG2b (GK14.1) specifically bound to substrate-supported planar membranes composed of dipalmitoylphosphatidylcholine (DPPC) and trinitrophenylaminocaproyldipalmitoylphosphatidylethanolamine (TNP-cap-DPPE). The equilibrium dissociation constants for sFc gamma RII at GK14.1-coated TNP-cap-DPPE/DPPC planar membranes containing 0.5-25 mol% TNP-cap-DPPE were approximately 1 microM. Total internal reflection with fluorescence photobleaching recovery was used to examine the dissociation kinetics. The fluorescence recovery curves were better described as a sum of two exponentials rather than by one exponential; the rates and fractional recoveries were approximately 1 s-1 (65%) and approximately 0.1 s-1 (35%). The similarity between the values of these equilibrium and kinetic parameters to those previously measured for the binding of IgG in solution to intact mouse Fc gamma RII reconstituted into planar membranes suggests that conformational changes which may occur when IgG is constrained to a membrane surface do not significantly affect the equilibrium or kinetics of IgG-mouse Fc gamma RII binding. The stoichiometry of sFc gamma RII-GK14.1 binding was 1:4, indicating that a significant fraction of the membrane-bound antibodies were not accessible for receptor binding. Possible mechanisms that might underlay the observed heterogeneity in sFc gamma RII-IgG binding kinetics are discussed.     

Feline ocular epithelial response to growth factors in vitro

OBJECTIVE: To examine the proliferative abilities of growth factors known to participate in wound healing on feline lens, iris pigment, ciliary, and retinal pigment epithelium cultured in vitro. ANIMALS: 8 clinically normal cats. PROCEDURE: Iris pigment, lens, ciliary, and retinal pigment epithelia of normal eyes of cats were isolated and cultured. Morphologic characteristics of primary cell cultures were studied by light and electron microscopy. Subcultures of epithelial cells were exposed to media supplemented with 0.5% fetal bovine serum plus various combinations of insulin and/or growth factors, including transforming growth factor-alpha, epidermal growth factor, acidic fibroblast growth factor, and basic fibroblast growth factor. Growth promoting effects were evaluated by counting with an electronic cell counter. RESULTS: Cells retained many of the morphologic characteristics of in vivo cells. Cell proliferation assays indicated that transforming growth factor-alpha stimulated lens and ciliary epithelial cell growth, and epidermal growth factor enhanced lens and iris pigment epithelial cell growth. Acidic fibroblast growth factor had proliferative effects on lens, iris pigment, and ciliary epithelium. Basic fibroblast growth factor was the most potent stimulator of all mitogens used, and caused substantial proliferation in all cell types. Insulin alone stimulated lens and ciliary epithelial proliferation but, combined with other growth factors, had a synergistic effect with those causing cell proliferation, except acidic fibroblast growth factor with iris pigment epithelium. CONCLUSION: Morphologic studies support the argument that pigment-producing cells are involved in feline ocular sarcoma. Growth factor studies indicated that ciliary epithelium has the most profound proliferative effect of all growth factors used. These data may help guide future studies in determining the cell of origin for feline ocular sarcoma.     

Basic fibroblast growth factor as one of the essential factors regulating lens transdifferentiation of pigmented epithelial cells

In vitro transdifferentiation of retinal pigmented epithelial cells of the chick embryo into lens cells can be markedly enhanced by culture in the presence of testicular hyaluronidase and phenylthiourea. Since the commercial preparations of hyaluronidase that had previously been used were very crude, a search for the actual effective molecule(s) enhancing lens transdifferentiation was conducted. First, we purified the enzyme and tested the effect of the purified hyaluronidase. Highly purified hyaluronidase itself did not enhance lens transdifferentiation. The crude hyaluronidase was then separated according to affinity with heparin, considering the possibility that the fibroblast growth factor (FGF) is contained in the crude hyaluronidase. Transdifferentiation-enhancing activity was detected in the fraction which was bound to heparin and eluted with 2 M NaCl, where no hyaluronate-degrading activity existed. Analysis of the fraction by SDS-PAGE revealed the existence of an 18 kDa protein whose NH2-terminal sequence was identical to that of basic FGF. The basic FGF derived from bovine brain also enhanced lens transdifferentiation of pigmented epithelial cells. These findings suggest that basic FGF must play a major role in enhancing transdifferentiation of pigmented epithelial cells to lens cells.     

Circulating factors as markers and mediators of endothelial cell dysfunction in preeclampsia

3 different types of complex spinal trauma are defined: Type I means a multilevel contiguous or non contiguous unstable injury, type II is described as a spinal injury with concomitant thoracic or abdominal lesion, type III stands for the coincidence of spinal injury and polytrauma. Overlapping of different types occurs. Type I: The incidence amounts according a german multicenter study to about 2.5%. Multilevel injuries need to be stabilized for a long distance from posterior. With a thorough analysis the segments to be fused are determined. Type II: The leading thoracic injury is a lung contusion which occurs in up to 50% of the cases. A CT scan of the thorax during the first diagnostic screening is recommended. Early reduction and stabilization from posterior should be aimed at. During the first two weeks anterior procedures are contraindicated. Abdominal injuries are to be found in 3-4% of all spinal injuries. All organs could be affected. A typical constallation is the "seat-belt syndrome" with lesions of the upper abdominal organs and a flexiondistraction injury of the upper lumbar spine. The main problem is to make the diagnosis of both components initially. Most of the patients may be treated in one operation by first taking care of the abdominal injury and than stabilizing the spine. The prognosis of this combination is favorable. Type III: In 17-18% of all polytraumatized patients lesions of the spine are to be diagnosed. From these only one third need surgical care. From 680 patients with operatively treated fractures of the thoracolumbar junction 6.2% were polytraumatized according to the multicenter study mentioned above. The risk of missing a spinal injury in polytrauma totals approximately 20%. Surgical stabilization should be performed in the primary phase (day-1-surgery). Additional injuries, potentially time consuming operations with a high blood loss sometimes necessitate a different approach. Non stabilized spinal injuries apparently do not have the same negative effect on the whole organism as long bone fractures. In the early phase of treatment on the C-spine only anterior procedures and on the thoracolumbar spine only posterior techniques should be applied.     

The localization of transforming growth factor alpha and epidermal growth factor receptor in stromal and epithelial compartments of developing human prostate and hyperplastic, dysplastic, and carcinomatous lesions

To gain insight into autocrine/paracrine mechanisms that may influence normal and abnormal growth of the human prostate, we studied the immunohistochemical localization of transforming growth factor alpha (TGF-alpha) and epidermal growth factor receptor (EGFr) in fetal, neonatal, prepubertal, and young adult glands. Results were compared with findings in specimens of benign prostatic hyperplasia (BPH), dysplasia (prostatic intraepithelial neoplasia--PIN), and carcinoma. EGFr was strongly and exclusively expressed in fetal basal cells, whereas TGF-alpha was localized in these and secretory cells as well as in differentiating smooth muscle cells. In neonatal and prepubertal glands, EGFr continued to be found only in basal cells, whereas TGF-alpha was now present in smooth muscle and infrequently in secretory cells. In the normal adult prostate, the receptor was strictly localized in basal cells and in the lateral plasma membranes of secretory cells, whereas its ligand was exclusively expressed in smooth muscle. This pattern persisted in PBH, but both EGFr and TGF-alpha staining appeared to be enhanced in their respective cellular compartments. Irrespective of grade, in dysplasia diffuse-moderate EGFr and strong TGF-alpha staining were both present in a majority of secretory cells. Similarly, most cells in Gleason grade 3 and 4 carcinomas expressed both EGFr and TGF-alpha. Our findings suggest that an unregulated paracrine mode of growth attends the development of BPH, whereas malignant transformation and progression involves autocrine/paracrine mechanisms reminiscent of those found in the developing prostate.     

Lovastatin-induced apoptosis in prostate stromal cells

Benign prostatic hyperplasia (BPH) is a common disease of aging men. Current medical treatment for this condition is only partially effective, therefore many patients must undergo surgery for symptomatic relief. BPH is caused by an increase in prostate epithelial and stromal cells, especially the latter. Since BPH stromal cells have a long life span and are not very responsive to androgen withdrawal, cultured BPH stromal cells were used to explore the feasibility of pharmacologically inducing apoptosis in these cells. We obtained BPH tissue during surgery, and stromal cells were isolated and maintained in culture. After cells achieved confluence, we induced apoptosis with the HMGCoA reductase inhibitor, lovastatin (30 micromol/L). The effects of testosterone (100 micromol/L), dihydrotestosterone (DHT; 100 micromol/L) and finasteride (100 micromol/L) on lovastatin-induced apoptosis were studied on cells grown in media containing charcoal stripped serum. Similarly, we examined the effect of the cholesterol pathway metabolites, mevalonic acid (30 micromol/L), geranyl geraniol (30 micromol/L), farnesol (10 micromol/L), squalene (30 micromol/L) and 7-ketocholesterol (3 micromol/L) on lovastatin-induced apoptosis. We demonstrated apoptosis by DNA laddering in agarose gels, by fluorescence microscopy following acridine orange staining, and by flow cytometry after end-labeling of DNA strand breaks with biotin-16-dUTP using deoxynucleotidyl exotransferase (TdT). Lovastatin at 30 micromol/L, but not at lower concentrations, induced apoptosis in BPH prostate stromal cells. This was seen (by flow cytometry) in 16.6 +/- 7.3% (mean +/- SD) of BPH cells treated with lovastatin at 72 h vs. 2.5 +/- 1.2% of cells treated with ethanol. Lovastatin-induced apoptosis was not increased in stripped serum or by the addition finasteride, and was not inhibited by testosterone or DHT. Only mevalonate and geranyl geraniol, prevented lovastatin-induced apoptosis whereas farnesol, squalene, or 7-ketocholesterol did not. We conclude that lovastatin can induce apoptosis in BPH stromal cells in vitro, and this is not affected by androgen withdrawal or stimulation. It is unlikely that lovastatin, per se, will be an effective treatment for BPH in vivo, but it does provide a means for inducing apoptosis in vitro. Understanding the apoptotic process in BPH stromal cells ultimately may lead to new therapeutic strategies for BPH.     

Expression of androgen receptor and growth factors in premalignant lesions of the prostate

To examine whether the expression pattern of fast-muscle type troponin-T (TnT) isoforms was fixed in cell lineage, breast muscle pieces (pectoralis major) from chick embryos and young and adult chickens were grafted on to chorio-allantoic membrane of 9-day-old chick embryos and cultured until the host embryos hatched out. Muscle fibre formation of the grafts was investigated by histological and immunohistochemical methods with anti-fast-muscle type and anti-slow-muscle type TnT sera, and the expression of fast-muscle type TnT in the grafts from chick embryos and young chickens was studied by SDS-polyacrylamide gel electrophoresis (SDS-PAGE), two-dimensional SDS-PAGE, and immunoblotting. In the chorio-allantoic grafting, the breast muscle initially degenerated forming pyknotic nuclei and hyaline cytoplasm. The surviving cells, which were supposed to be satellite cells, regenerated new muscle fibres of the same type as those of the grafted muscle in respect of TnT isoform expression. Therefore, we considered that the ability to express specific isoforms of TnT was fixed in the satellite cells, and that chorio-allantoic grafting was a useful technique for studying muscle differentiation.     

Studies on the expression of fibroblast growth factors and fibroblast growth factor receptors in human prostate cancer

PURPOSE: We tried to clarify the role of fibroblast growth factors (FGFs) and those receptors (FGF-Rs) in cell proliferation of human prostate cancer. METHODS: The mRNA expression of FGF1, FGF2, FGF7, FGF-R1, FGF-R2 (IIIb), and FGF-R2 (IIIc) was investigated by RT-PCR in androgen sensitive cells (LNCaP), androgen-independent cells (PC3) and primary cultured stromal (PS) and epithelial cells (PE) from benign prostatic hyperplasia (BPH). Expression of the mRNA of FGF-R1, FGF-R2 (IIIb) and FGF-R2 (IIIc) in human prostate cancer tissue was similarly analyzed. Furthermore, the level of FGF-R1 expression in human prostate cancer was measured by semi-quantitative RT-PCR. RESULTS: FGF-R1 mRNA was detected in LNCaP, PC3 and the primary cultured stromal cells of BPH. FGF-R2 (IIIb) was seen in LNCaP cells and the primary cultured epithelial cells of BPH, while FGF-R2 (IIIc) was only observed in PC3. FGF1 mRNA was expressed in LNCaP and PC3, while FGF2 mRNA was in PC3 alone. The expression of FGF7 mRNA was detected only in the primary cultured stromal cells. Of 17 patients with human prostate cancer, FGF-R2 (IIIb) was detected in 2 and FGF-R2 (IIIc) in 15. Histological type of two cases having FGF-R2 (IIIb) were well differentiated adenocarcinoma. The mRNA levels of FGF-R1 in poorly and moderately differentiated types were significantly higher than those in well differentiated ones (p < 0.05). CONCLUSION: These findings suggest that several changes of expression in FGFs and FGF-Rs may correlate with malignant progression of human prostate cancer.     

Peptide growth factors regulate insulin-like growth factor binding protein production by fetal rat lung fibroblasts

Insulin-like growth factor (IGF) binding proteins (IGFBPs) are expressed in fetal lung and may provide important post-translational regulation of IGF-induced mitogenesis during lung organogenesis. Because of the observation that growth factors can control cell growth through regulation of IGFBPs, we examined IGFBP production by fetal lung fibroblasts following stimulation by peptide growth factors important for fetal lung growth and development. Fetal lung fibroblasts were cultured in serum-free medium supplemented with various growth factors for up to 48 h, and IGFBPs in conditioned medium (CM) were analyzed by ligand blot and immunoblot techniques. Accumulation of CM IGFBP-3 was increased and IGFBP-2 decreased by incubation with either keratinocyte growth factor (KGF) or epidermal growth factor (EGF). The effect of these factors on IGFBP-3 accumulation increased with time but the effects of KGF on CM IGFBP-2 decreased over 48 h of incubation. CM IGFBP-4 was increased by 24 and 48 h incubation with basic fibroblast growth factor (bFGF; 2.1- and 2.7-fold increases at 24 and 48 h, respectively) and platelet-derived growth factor-BB (PDGF-BB; 4.2- and 14.9-fold increases at 24 and 48 h, respectively), and 48 h incubation with EGF (6.3-fold increase). In 48-h coincubation experiments, EGF in combination with PDGF-BB or with bFGF, and bFGF in combination with PDGF-BB, resulted in IGFBP-4 accumulations twice that expected from a summation of the effects of either growth factor alone (IGFBP-4 increased 9.8-, 4.0-, and 1.8-fold by PDGF-BB, EGF, and bFGF, respectively; and 27.1-, 37.3-, and 13.0-fold by PDGF-BB plus EGF, PDGF-BB plus bFGF, and EGF plus bFGF, respectively). These results suggest synergistic effects of these growth factors on IGFBP-4 accumulation in fetal lung fibroblast CM. Because IGFBPs are known to regulate DNA synthesis, we speculate that peptide growth factors may alter cell proliferation in fetal lung, in part through their effect on IGFBPs.     

Interplay between sex steroids and melatonin in regulation of human benign prostate epithelial cell growth

Human benign prostatic epithelial cells contain functional melatonin receptors that can suppress cell growth and viability. The development of benign prostatic hyperplasia in men is assumed to result from androgen-estrogen imbalance. The impact of sex steroids on melatonin receptors in human benign prostate epithelial cells was investigated. The suppression by melatonin of [3H]thymidine incorporation and cGMP, and the enhancement of cAMP levels in the cells were used as markers of melatonin responses. Dihydrotestosterone (DHT) and 17 beta-estradiol (E2) separately increased [3H]thymidine incorporation into the cells, but suppressed it when combined. In cells grown with DHT, melatonin responses were extenuated. E2 greatly reduced the apparent affinity of [125I]melatonin binding in these cells without affecting binding site density. In parallel, the ability of melatonin to suppress [3H]thymidine incorporation into the cells was ablated within 1 h after the addition of E2. The melatonin-mediated increase in cAMP and decrease in cGMP concentrations were also ablated by E2. Preincubation of the cells with bis-indolylmaleimide (GF 102903X), a specific inhibitor of protein kinase C, prevented the E2-mediated inactivation of melatonin binding and the inhibitory action on [3H]thymidine incorporation. Prolonged (18-h) incubation of the cells with phorbol 12-myristate 13-acetate to down regulate protein kinase activity, partially restored [125I]melatonin binding and responsiveness in the E2-treated cells. These data indicate that 1) DHT and E2 enhance prostate epithelial cells growth, but reduce cell growth when combined; 2) DHT extenuates the inhibitory effects of melatonin on epithelial cell growth; and 3) E2 acts to inactivate melatonin receptors and consequently responses in human epithelial benign prostatic hyperplasia cells. This process is probably mediated by protein kinase C. Together, these results show an interplay between melatonin and sex steroids in the regulation of benign prostatic epithelial cell growth.     

Concentrations of specific epithelial growth factors in the urine of interstitial cystitis patients and controls

PURPOSE: Interstitial cystitis (IC) is a chronic bladder disease for which the etiology is unknown. Because the bladder epithelium is often abnormal in IC, we determined whether the levels of specific urine growth factors postulated to be important for bladder epithelial proliferation are altered in IC. MATERIALS AND METHODS: ELISAs were used to determine levels of epidermal growth factor (EGF), insulin-like growth factor 1 (IGF1), insulin-like growth factor binding protein 3 (IGFBP3), and heparin binding epidermal growth factor-like growth factor (HB-EGF) in urine specimens from women with IC, asymptomatic women without bladder disease, and women with bacterial cystitis. RESULTS: Urine HB-EGF levels were specifically and significantly decreased in IC patients as compared to asymptomatic controls or patients with bacterial cystitis, whether expressed as concentration (amount per volume of urine) or the amount relative to urine creatinine in each specimen. In contrast, urine EGF, IGF1, and IGFBP3 levels were all significantly elevated in IC patients compared to asymptomatic controls. Further, the amounts of urine EGF and IGF1 were also elevated in IC patients as compared to patients with bacterial cystitis, and urine IGFBP3 levels were significantly elevated when expressed per milligram of urine creatinine. CONCLUSIONS: These findings indicate that complex changes in the levels of urine epithelial cell growth factors (EGF, IGF1, and HB-EGF) and a growth factor binding protein (IGFBP3) are associated with IC. While EGF, IGF1, and IGFBP3 levels are either the same or increased in the urine of IC patients as compared to patients with bacterial cystitis or asymptomatic controls, HB-EGF levels are significantly decreased in the urine of IC patients. Understanding the reasons for these changes may lead to understanding the pathogenesis of this disorder.     

Peptide and lipid growth factors decrease cis-diamminedichloroplatinum-induced cell death in human ovarian cancer cells

Growth factors have been demonstrated to regulate the proliferation and viability of a number of cell lineages. Because most drugs used in chemotherapy kill cells through programmed cell death, by the process of apoptosis, we determined whether growth factors, specifically epidermal growth factor (EGF) and lysophosphatidic acid (LPA), which we have demonstrated recently to be a potent growth factor for ovarian cancer cells, would alter the ability of cis-diamminedichloroplatinum (cis-DDP), the most effective chemotherapeutic agent for ovarian cancer, to kill the HEY ovarian cancer cell line. We demonstrate that both EGF and LPA decrease the ability of cis-DDP to kill HEY ovarian cancer cells as assessed by colony-forming cell activity and dye reduction. Morphological changes, DNA release, and electron microscopy suggested that LPA and EGF protect ovarian cancer cells from programmed cell death induced by cis-DDP. Because LPA is present in high levels in ascitic fluid from ovarian cancer patients, and the EGF receptor is expressed by tumor cells from a significant portion of patients where it correlates with prognosis, growth factor modulation of cis-DDP-induced apoptosis may play a role in the poor prognosis associated with ovarian cancer.     

Lack of effect of hematopoietic growth factors on human breast epithelial cell growth in serum-free primary culture

A number of recombinant cytokines believed to regulate normal hematopoiesis are now being used in cancer treatment protocols to reduce the myelosuppressive toxicity of intensive chemoradiotherapy regimens. It is widely assumed that such cytokines are relatively specific for hematopoietic cells, although some cell lines derived from a variety of non-hematopoietic human tumors can respond to some of these factors. However, relatively little is known about their ability to stimulate (or inhibit) the proliferation of freshly isolated normal or malignant non-hematopoietic cells. We have used a serum-free culture medium that selectively supports the growth of human breast epithelial cells (HBEC) obtained directly from normal or malignant tissue samples to evaluate potential stimulatory or inhibitory effects of eight cytokines: granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, Steel factor, interleukin-2, interleukin-3, interleukin-6, transforming growth factor-beta and macrophage inflammatory protein-1 alpha, on these cells cultured both in the presence of epidermal growth factor, a potent stimulator of HBEC growth, and in its absence. HBEC growth was assessed after 7 and 14 days using the tetrazolium-dye reduction assay. Potential effects on the well studied MCF-7 breast cancer cell line, cultured under the same conditions, were also investigated. None of the cytokines (which were tested over a wide range of concentrations) had any modulating effect on the growth of normal or malignant HBEC under the conditions used with the exception of transforming growth factor-beta, which was consistently and significantly inhibitory.(ABSTRACT TRUNCATED AT 250 WORDS)