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Michael Koutsilieris

Publications and source records attributed to Michael Koutsilieris.

At least 19 recordsLinked to original sources
PubMed2006

Molecular detection of tyrosinase transcripts in peripheral blood from patients with malignant melanoma: correlation of PCR sensitivity threshold with clinical and pathologic disease characteristics.

BACKGROUND: Positive molecular detection of tyrosinase transcripts (TYR mRNA) in RNA extracts of peripheral blood (PB) samples from patients with malignant melanoma provides evidence of disease dissemination. METHODS: Total RNA extracted from PB was quantified and subjected to RT-PCR under ultra-sensitive and reduced-sensitivity PCR conditions using SSRT-II. Positive TYR mRNA detection in 78 melanoma patients and 40 healthy volunteers was correlated with clinical stage, Breslow's evaluation of tumor thickness, Clark's assessment of tumor invasion, the location of the primary tumor site, and tumor histology. The assay sensitivity was evaluated by spiking PB with the melanoma cell line SK-MEL-28. RESULTS: Using ultra-sensitive PCR conditions, eight out of 40 RNA (20%) samples from healthy volunteers and 50 out of 78 RNA (64.1%) samples from melanoma patients tested positive. Using reduced-sensitivity PCR conditions, we found only two positives in 40 RNA samples from healthy subjects and 20 positives in 78 RNA samples (25.6%) from melanoma patients. Only positive PCR samples for the reduced-sensitivity PCR assay correlated significantly with stage IV (metastatic) disease (p=0.0395). There was no significant correlation between positive TYR mRNA samples for either PCR condition (ultra-sensitive and reduced-sensitivity) with Breslow's classification of tumor thickness, Clark's assessment of tumor invasion, location of the primary tumor site, and type of tumor histology. CONCLUSIONS: We conclude that reduced-sensitivity rather than ultra-sensitive PCR conditions correlate with clinical stage in melanoma patients.

Adult↗
PubMed2006

Combination therapy using LHRH and somatostatin analogues plus dexamethasone in androgen ablation refractory prostate cancer patients with bone involvement: a bench to bedside approach.

The development of resistance to anticancer therapies is a major hurdle in preventing long-lasting clinical responses to conventional therapies in hormone-refractory prostate cancer. Herein, the molecular evidence documenting that bone metastasis microenvironment survival factors (mainly the paracrine growth hormone-independent, urokinase-type plasminogen activator-mediated increase of IGF-1 and the endocrine production of growth hormone-dependent IGF-1, mainly liver-derived IGF-1 production) produce an epigenetic form of prostate cancer cells that are resistant to proapoptotic therapies is reviewed. Consequently, the authors present the conceptual framework of a novel antibone microenvironment survival factor, mainly an anti-IGF-1 hormonal manipulation for androgen ablation refractory prostate cancer (a combination of conventional androgen ablation therapy [luteinising hormone-releasing hormone agonist-A or orchiectomy]) with dexamethasone plus somatostatin analogue, which yielded durable objective responses and major improvement of bone pain and performance status in stage D3 prostate cancer patients.

Adenocarcinoma↗
PubMed2005

The glutamatergic system outside the CNS and in cancer biology.

Glutamate is a major excitatory neurotransmitter in the CNS. The signalling machinery consists of: glutamate receptors, which are responsible for signal input; plasma glutamate transporters, which are responsible for signal termination; and vesicular glutamate transporters for signal output through exocytic release. Recently, data have suggested that the glutamatergic system plays an important role in non-neuronal tissues. In addition, the expression of glutamatergic system has been implicated in tumour biology. This review outlines the evidence, which suggests that the glutamatergic system may have an important role in cancer biology.

Amino Acid Transport System X-AG↗
PubMed2004

Combination of somatostatin analog, dexamethasone, and standard androgen ablation therapy in stage D3 prostate cancer patients with bone metastases.

PURPOSE: Androgen ablation-refractory prostate cancer patients (stage D3) develop painful bone metastases and limited responsiveness to conventional therapies, hence the lack of universally accepted "gold standard" treatment for this poor prognosis clinical setting. We tested the safety and efficacy in stage D3 patients of the combination hormonal therapy, which combines administration of somatostatin analog and dexamethasone with standard androgen ablation monotherapy (luteinizing-hormone releasing-hormone analog or orchiectomy). EXPERIMENTAL DESIGN: Thirty eight patients with stage D3 prostate cancer (mean age 71.8 +/- 5.9 years) continued receiving androgen ablation therapy in combination with oral dexamethasone (4 mg daily for the 1st month of treatment, tapered down to 1 mg daily by the 4th month, with 1 mg daily maintenance dose thereafter) and somatostatin analog (20 mg octreotide i.m. injections every 28 days). RESULTS: Twenty-three of 38 patients (60.5%) receiving this combination regimen had partial responses [PR, >/=50% prostate-specific antigen (PSA) decline], 9 (21.1%) had stable disease, and 7 (18.4%) had progressive disease. In 47.7% (18 of 38) of patients, their serum PSA levels decreased with treatment but did not return to their respective baselines until the end of follow-up (or death from non-prostate cancer-related causes). The median time-to-return to baseline PSA was 12 months (95% CI, 7-17 months), median progression-free survival was 7 months (95% CI, 4.5-9.5 months), median overall survival was 14 months (95% CI, 10.7-17.4 months), and median prostate cancer-specific overall survival (defined as time from onset of combination therapy until prostate cancer-related death) was 16.0 months (95% CI, 11.9-20.1 months). All patients reported significant and durable improvement of bone pain and performance status (for a median duration of 14 months; 95% CI, 9-19 months), without major treatment-related side effects. We observed a statistically significant (P < 0.01) reduction in serum insulin-like growth factor-1 levels at response to the combination therapy. T levels remained suppressed within castration levels at baseline and throughout therapy, including relapse. CONCLUSION: The combination therapy of dexamethasone plus somatostatin analog and standard androgen ablation manipulation produces objective clinical responses and symptomatic improvement in androgen ablation-refractory refractory prostate cancer patients.

Aged↗
PubMed2004

Bone microenvironment-related growth factors modulate differentially the anticancer actions of zoledronic acid and doxorubicin on PC-3 prostate cancer cells.

OBJECTIVES: We analyzed the actions of zoledronic acid (10-250 microM) and doxorubicin (10-250 nM) on PC-3 prostate cancer cells using both continuous (48-96 hr) and pulsatile exposures (15 min/day for up to three consecutive days). RESULTS: The proliferation of PC-3 cells was inhibited by either continuous or pulsatile exposures of zoledronic acid in a dose-dependent manner. In contrast, pulsatile exposures of doxorubicin failed to inhibit the growth of PC-3 cells. In addition, the inhibition of PC-3 cells by zoledronic acid was partially neutralized by exogenous administration of geranylgeranyl pyrophosphate (GGPP), however, not by farnesyl pyrophosphate (FPP). Furthermore, exogenous administration of transforming growth factor beta 1 (TGF-beta1), interleukin 6 (IL-6), basic fibroblast growth factor (bFGF), and more potently, insulin-like growth factor 1 (IGF-1) inhibited the doxorubicin-induced apoptosis of PC-3 cells. Under identical experimental conditions, these growth factors failed to alter the cytotoxicity of PC-3 cells induced by zoledronic acid. CONCLUSIONS: These data suggest that (i) repetitive and pulsatile (15 min/day) exposure to zoledronic acid inhibited the growth of PC-3 cells, (ii) this anticancer action of zoledronic acid was partially mediated by the attenuation of GGPP production, and (iii) bone microenvironment-related growth factors do not alter the anticancer actions of zoledronic acid on PC-3 cells.

Antibiotics, Antineoplastic↗
PubMed2004

Molecular staging by RT-pCR analysis for PSA and PSMA in peripheral blood and bone marrow samples is an independent predictor of time to biochemical failure following radical prostatectomy for clinically localized prostate cancer.

Radical prostatectomy should ideally be curative for all patients with clinically localized prostate cancer (PrCa), yet a sizeable proportion of them eventually relapse. We examined in this setting the feasibility of pre-operative risk stratification for early post-operative relapse using reverse transcriptase polymerase chain reaction (RT-PCR) for prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) transcripts in preoperative bone marrow (BM) biopsies and peripheral blood (PBL) samples. Nested RT-PCR for PSA and PSMA transcripts were performed in RNA from BM biopsies and PBL samples prospectively obtained from 111 men newly diagnosed, by trans-rectal ultrasound (TRUS)-guided biopsy, with clinically localized PrCa and scheduled to undergo radical prostatectomy, according to their respective doctors' recommendation. Molecular analysis for each sample (PBL or BM) was considered positive only if both PSA and PSMA transcripts were detectable. Serial serum PSA level measurements served for biochemical follow-up and detection of biochemical failure (PSA >0.2 ng/ml). PBL and BM RT-PCR molecular staging delineated three groups of patients (a) PBL-BM- (72 patients, 65%), (b) PBL+BM+ (29 patients, 26%), and (c) PBL+BM- (10 patients, 9%). These three groups corresponded to low, high, and intermediate risk for early post-prostatectomy recurrence (median time to biochemical failure of >38, 8, and >28 months, respectively). Multivariate analysis confirmed that molecular staging status was independent predictor of disease-free survival, after adjusting for PSA levels and Gleason score. In clinically localized PrCa, combined PSA/PSMA RT-PCR in PBL and BM is an independent predictor of time to biochemical failure following radical prostatectomy.

Antigens, Surface↗
PubMed2004

Combination of LHRH analog with somatostatin analog and dexamethasone versus chemotherapy in hormone-refractory prostate cancer: a randomized phase II study.

OBJECTIVES: To evaluate prospectively the combination of a luteinizing hormone-releasing hormone analog with a somatostatin analog and dexamethasone in patients with hormone-refractory prostate cancer (HRPC) in a randomized Phase II study. HRPC presents a challenging therapeutic problem. Salvage chemotherapy is the usual approach at this stage of the disease. The combination of a luteinizing hormone-releasing hormone analog with a somatostatin analog and dexamethasone has produced objective clinical responses in HRPC. METHODS: Forty patients with HRPC were randomized to receive one of two treatments. Group 1 underwent chemotherapy (estramustine 140 mg three times daily and etoposide 100 mg orally for 21 days) and group 2 the combination of a somatostatin analog (lanreotide 30 mg intramuscularly every 14 days) and dexamethasone (4 mg tapered to 1 mg), in addition to androgen ablation by orchiectomy or a luteinizing hormone-releasing hormone analog (triptorelin 3.75 mg intramuscularly every 28 days). The clinical and prostate-specific antigen (PSA) response, overall survival, time to progression, and toxicity were compared between the two groups. RESULTS: The data of 20 patients in group 1 and 18 in group 2 were analyzed. The demographic and clinical data were similar in the two groups at study entry. A PSA response (decrease of greater than 50%) was observed in 45% of group 1 and 44% of group 2. The difference was not statistically significant. A partial clinical response was observed in 29% and 30% of groups 1 and 2, respectively. Again, the difference was not statistically significant. Changes in performance status and pain score during treatment were not significantly different in the two groups. Hematologic toxicity was more frequent in group 1 (80% of patients), and mild diabetes was more frequent in group 2 (22% of patients). The overall survival was 18.8 months in group 1 and 18 months in group 2 (not statistically significant). The time to progression was 6 versus 4 months and, in the PSA responder subgroup, it was 8 versus 7.7 months in groups 1 and 2, respectively (neither difference was statistically significant). CONCLUSIONS: The results of our randomized Phase II study indicated that the new combination treatment (luteinizing hormone-releasing hormone analog, somatostatin analog, and dexamethasone) may be equally effective as salvage chemotherapy in patients with HRPC in terms of the clinical and PSA response, overall survival, and time to progression. A larger prospective Phase III trial is required to confirm our observations.

Adenocarcinoma↗
PubMed2004

The Akt pathway: molecular targets for anti-cancer drug development.

The serine/threonine kinase Akt functions intracellularly as a cardinal nodal point for a constellation of converging upstream signaling pathways, which involve stimulation of receptor tyrosine kinases such as IGF-1R, HER2/Neu, VEGF-R, PDGF-R), and an assembly of membrane-localized complexes of receptor-PI-3K and activation of Akt through the second messenger PIP(3). The integration of these intracellular signals at the level of Akt and its kinase activity, regulates the phosphorylation of its several downstream effectors, such as NF-kappa B, mTOR, Forkhead, Bad, GSK-3 and MDM-2. These phosphorylation events in turn mediate the effects of Akt on cell growth, proliferation, protection from pro-apoptotic stimuli, and stimulation of neo-angiogenesis. Because Akt and its upstream regulators are deregulated in a wide range of solid tumors and hematologic malignancies, and in view of the aforementioned biologic sequelae of this pathway, the Akt pathway is considered a key determinant of biologic aggressiveness of these tumors, and a major potential target for novel anti-cancer therapies. This review focuses on ongoing translational efforts to therapeutically target Akt and its biologic sequelae, either at the level of Akt itself or at the levels of its upstream regulators and downstream effectors. Because Akt is also important for proliferative and anti-apoptotic signaling pathways critical for normal cells, particular emphasis is placed on the fine-tuning the targeting of individual components of this pathway to maximize the therapeutic index of anti-cancer strategies based on the PI-3K/Akt pathway.

Animals↗
PubMed2003

Mutation analysis of BrCA1, BrCA2, and p53 versus soluble HLA class I and class II in a case of familial endometriosis.

OBJECTIVE: To investigate possible correlation(s) between mutations of BrCA1, BrCA2, and p53 genes versus soluble HLA expression in familial endometriosis. DESIGN: Mutation analysis. SETTING: University teaching departments and hospital. PATIENT(S): A family with seven women in two generations with familial endometriosis. INTERVENTION(S): Mutation analysis of BrCA1, BrCA2, and p53 genes. MAIN OUTCOME MEASURE(S): A point mutation of the BrCA1 gene appears to inhibit soluble HLA secretion. RESULT(S): Among the three genes examined, only the BrCA1 gene showed a T to A mutation at position 3232 that correlates with total abolishment of both class I and class II antigen release. CONCLUSION(S): A possible correlation between a BrCA1 mutation and soluble HLA expression appears to exist. The mutation is not stage dependent and seemingly influences the secretion of both class I and class II antigens that are totally absent from the serum of only one family member.

Aged↗
PubMed2003

Urokinase-type plasminogen activator and insulin-like growth factor-binding protein 3 mRNA expression in endometriotic lesions and eutopic endometrium: implications for the pathophysiology of endometriosis.

The peritoneal fluid of women with endometriosis contains an increased insulin-like growth factor 1 (IGF-1) bioavailability, which is produced by limited hydrolysis of urokinase-type plasminogen activator (uPA) on IGF-binding protein 3 (IGFBP-3). Recently, IGF-1 was shown to inhibit apoptosis of endometrial-like cells in vitro, suggesting that a microenvironment of increased IGF-1 bioavailability can optimize the survival of endometrial cells grown ectopically. Here the expression of mRNA of IGFBP-3 and uPA in tissue biopsies from eutopic endometrium and endometriotic lesions obtained at laparoscopy from women with endometriosis have been analyzed, and it is documented that both IGFBP-3 and uPA mRNA expression are increased from 3- to 10-fold in endometriotic lesions versus eutopic endometrium. Consequently, the necessary components (uPA and IGFBP-3 expression) of endocrine/autocrine/paracrine enhancement of local IGF bioavailability mediated by uPA hydrolysis of the IGFBP-3 were present in endometriotic lesions. These data possibly explain the origin of the increased content of uPA activity, IGF-1 bioavailability, and NH(2)-truncated forms of IGFBP-3 in the peritoneal fluid of women with endometriosis.

Ascitic Fluid↗
PubMed2003

Growth hormone-releasing hormone and extra-pituitary tumorigenesis: therapeutic and diagnostic applications of growth hormone-releasing hormone antagonists.

Growth hormone-releasing hormone (GHRH) regulates growth hormone release from the pituitary. However, in addition to this neuroendocrine action, much evidence implies an additional role for GHRH in carcinogenesis in non-pituitary tissues. This role of GHRH in cancer development appears to be due to the operation of several mechanisms, which involve the regulation of the growth hormone-dependent hepatic insulin-like growth factor I (IGFI) production, tumoural IGF-I and IGF-II secretion and direct action of GHRH on tumour cells by autocrine and/or paracrine pathways. This review summarises the available information regarding the role of GHRH in tumorigenesis with special emphasis on the direct action of GHRH in primary and experimental cancers.

Animals↗
PubMed2002

Human vascular endothelial cells with extended life spans: in vitro cell response, protein expression, and angiogenesis.

An in vitro angiogenesis system was designed for screening angiogenic agonists and antagonists. In order to obtain large quantities of cells and reproducibility, human endothelial cells with extended life spans were developed by retroviral transfection. The resulting cells grown in a serum-free medium containing endothelial cell growth supplement (ECGS) have a telomerase activity, extended life spans of at least 21 passages, and an endothelial cell phenotype (diI-acetylated-LDL upake, factor VIII-related antigen, VEGFR-1 and R-2, and tissue-type plasminogen activator (tPA)) that resembled that of unaltered primary endothelial cells. Exceptions were (i) a higher expression of tPA, and (ii) a non-significant growth response to FGF-2 or VEGF stimulation. Within three-dimensional fibrin gels, specific cell clones rapidly formed tubular structures in a more reproducible manner than those observed with low-passage primary cells. Tube formation by primary endothelial cells and those with extended life spans was dependent upon FGF-2 and ECGS, respectively. Both cell types produced FGF-2 and VEGF cytokines. Increasing doses of suramin significantly decreased the size of microvessels formed by both cell lines. These functional results indicate that a vascular matrix system containing human cells with extended life spans can be successfully utilized as an in vitro assay for antiangiogenic compounds.

Angiogenesis Inhibitors↗
PubMed2002

Combination of dexamethasone and a somatostatin analogue in the treatment of advanced prostate cancer.

The local microenvironment at the sites of cancer metastases protects tumour cells from anticancer drug-induced apoptosis via mechanisms, such as soluble growth factors and cytokines. The concept of antisurvival factor (ASF) therapy as a component of anticancer treatments aims at neutralising the protective effect conferred upon cancer cells by the survival factor(s) derived by the local microenvironment, in order to enhance the sensitivity and/or reverse the resistance of tumour cells to other anticancer therapeutic strategies. Herein, we review the translation of this concept from ex vivo studies to clinical applications in the setting of prostate cancer refractory to androgen ablation (stage D3). At this stage, which predominantly involves bone metastases, insulin-like growth factor 1 (IGF-1) production (either growth hormone (GH)-dependent or GH-independent) can protect tumour cells from apoptosis, despite the significant suppression of androgens. The application of the ASF therapeutic concept involves the combination of dexamethasone (which suppresses GH-independent IGF-1) and somatostatin analogue (which suppresses endocrine, GH-dependent IGF-1) with the pro-apoptotic effect of the testicular androgen suppression by sustained use of LHRH analogues. In stage D3, patients who had failed anti-androgen withdrawal, chemotherapy and also had several other adverse prognostic features, the ASF-based combination achieved durable objective responses and major symptomatic improvement, paving the way for future applications of this approach. The ASF-based combination therapy illustrates a novel paradigm in cancer treatment: anti-tumour treatment strategies may not only aim at directly inducing cancer cell apoptosis, but can also target the tumour microenvironment and neutralise the protection it confers on metastatic cancer cells. The favourable toxicity profile of this therapeutic approach calls for its testing in a randomised controlled setting in metastatic prostate cancer and, conceivably, in other IGF-1-responsive malignancies.

Androgen Antagonists↗
PubMed2002

Molecular evidence-based use of bone resorption-targeted therapy in prostate cancer patients at high risk for bone involvement.

BACKGROUND: To improve median survival of patients with prostate cancer that has metastasized to bone, we need to better understand the early events of the metastatic process in skeleton and develop molecular tools capable of detecting the early tumor cell dissemination into bones (micrometastasis stage). However, the initial phase of tumor cell dissemination into the bone marrow is promptly followed by the migration of tumor cells into bone matrix, which is a crucial step that signals the transformation of micrometastasis to macrometastasis stage and clinically evident metastasis. The migration of cancer cells into bone matrix requires the activation of local bone resorption. Such an event contributes to tumor cell hiding/ escaping from high immunologic surveillance of bone marrow cells. Within bone matrix, tumor cells are establishing plethoric cell-cell interactions with bone marrow-residing cells, ensuring their survival and growth. Recently, RT-PCR detections of tumor marker transcripts, such as PSA and PSMA mRNA performed in RNA extracts of peripheral blood nucleated cells and bone marrow biopsy, have enabled the stratification of patients with clinically localized prostate cancer being of high risk for extraprostatic disease and bone involvement. Therefore, it is conceivable that bisphosphonate blockade of bone resorption can inhibit the migration of tumor cells into bone matrix during the early phase of disease dissemination into bone marrow (micrometastasis stage). Consequently, assessment of the efficacy and efficiency of bisphosphonates to arrest the evolution of bone lesions in this particular clinical setting of patients with clinically localized prostate cancer and positive molecular staging status (high risk for bone involvement) is warranted.

Antineoplastic Agents↗
PubMedDate not supplied

Combined androgen blockade-induced anemia in prostate cancer patients without bone involvement.

BACKGROUND: To determine the onset and extent of combined androgen blockade (CAB)-induced anemia in prostate cancer patients without bone involvement. PATIENTS AND METHODS: Forty-two patients with biopsy-proven prostatic adenocarcinoma [26 with stage C (T3N0M0) and 16 with stage D1 (T3N1M0)] were included in this study. All patients received CAB [leuprolide acetate (LHRH-A) 3.75 mg, intramuscularly, every 28 days plus 250 mg flutamide, tid, per Os] and were evaluated for anemia by physical examination and laboratory tests at baseline and 4 subsequent intervals (1, 2, 3 and 6 months post-CAB). Hb, PSA and Testosterone measurements were recorded. Patients with stage D2-3 disease, abnormal hemoglobin level or renal and liver function tests that were higher than the upper limits were excluded from the study. The duration of the study was six months. RESULTS: The mean hemoglobin (Hb) levels were significantly declined in all patients from baseline of 14.2 g/dl to 14.0 g/dl, 13.5 g/dl, 13.2 g/dl and 12.7 g/dl at 1, 2, 3 and 6 months post-CAB, respectively. Severe and clinically evident anemia of Hb < 11 g/dl with clinical symptoms was detected in 6 patients (14.3%). This CAB-induced anemia was normochromic and normocytic. At six months post-CAB, patients with severe anemia had a Hb mean value of 10.2 +/- 0.1 g/dl (X +/- SE), whereas the other patients had mild anemia with Hb mean value of 13.2 +/- 0.17 (X +/- SE). The development of severe anemia at 6 months post-CAB was predictable by the reduction of Hb baseline value of more than 2.5 g/dl after 3 months of CAB (p = 0.01). The development of severe CAB-induced anemia in prostate cancer patients did not correlate with T baseline values (T < 3 ng/ml versus T > or = 3 ng/ml), with age (< 76 yrs versus > or = 76 yrs), and clinical stage (stage C versus stage D1). Severe and clinically evident anemia was easily corrected by subcutaneous injections (3 times/week for 1 month) of recombinant erythropoietin (rHuEPO-beta). CONCLUSION: Our data suggest that rHuEPO-beta correctable CAB-induced anemia occurs in 14.3% of prostate cancer patients after 6 months of therapy.

Adenocarcinoma↗
PubMedDate not supplied

Parathyroid hormone-related peptide and cardiovascular system.

The parathyroid hormone-related peptide (PTHrP) was initially identified in the early eighties, as the humoral mediator causing hypercalcaemia associated with malignancy. However, recently PTHrP was also shown to mediate a wide range of local paracrine/autocrine and intracrine functions in various tissues under physiological and pathological conditions. Indeed, PTHrP is a polyhormone, which can act through different receptors, including the type 1 parathyroid hormone (PTH) receptor 1 (PTH-1R). In the cardiovascular system, PTHrP appears to have potent effects on vascular smooth muscle cells and cardiomyocytes, where it participates in different pathological conditions, such as ischemia and heart failure. Therefore, it is conceivable that further studies on the regulation of PTHrP expression, characterization of its autocrine/paracrine/intracrine functions and definition of its intracellular signal transduction pathways in cardiomyocytes and cardiac vascular smooth muscle cells can elucidate the potential role of PTHrP in cardiovascular pathophysiology.

Cardiovascular Diseases↗
PubMedDate not supplied

Glucocorticoid receptor function suppresses insulin-like growth factor 1 activity in human KLE endometrial-like cells.

We analysed the glucocorticoid receptor (GR) regulation on the expression of insulin-like growth factor 1 (IGF-1), type I IGF receptor (IGF-1.R), IGF-binding protein 3 (IGFBP-3), urokinase-type plasminogen activator (uPA) and uPA receptor (uPA.R) mRNA in human KLE endometrial-like cells. We documented that KLE cells express IGF-1, IGF-1.R, uPA and IGFBP-3 mRNA, however not uPA.R mRNA. Exogenous administration of dexamethasone inhibited the proliferation of KLE cells without inducing apoptosis. The inhibition of dexamethasone on KLE cell proliferation was neutralized by exogenous administration of IGF-1. Furthermore, dexamethasone suppressed the expression of IGF-1 mRNA and IGF-1.R mRNA as well as the IGF-1 bioavailability in KLE cell culture media, but it did not alter the expression of uPA mRNA and IGFBP-3 mRNA in KLE cells. Since the peritoneal fluid of women with endometriosis is known to contain IGF-1, which stimulates the proliferation and inhibits the apoptosis of endometrial-like cells, it is conceivable that GR-mediated down-regulation of IGF-1 bioavailability may be of clinical relevance for endometriosis.

Cell Line↗