Mitostatin Is Down-Regulated in Human Prostate Cancer and Suppresses the Invasive Phenotype of Prostate Cancer Cells
Gardiman, Marina P.
Gomella, Leonard G.
Iozzo, Renato V.
Cancer cell migration
Tumor suppressor genes
Permanent link to this recordhttp://hdl.handle.net/20.500.12613/7097
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AbstractMITOSTATIN, a novel putative tumor suppressor gene induced by decorin overexpression, is expressed in most normal human tissues but is markedly down-regulated in advanced stages of mammary and bladder carcinomas. Mitostatin negatively affects cell growth, induces cell death and regulates the expression and activation levels of Hsp27. In this study, we demonstrated that ectopic expression of Mitostatin in PC3, DU145, and LNCaP prostate cancer cells not only induced a significant reduction in cell growth, but also inhibited migration and invasion. Moreover, Mitostatin inhibited colony formation in soft-agar of PC3 and LNCaP cells as well as tumorigenicity of LNCaP cells in nude mice. Conversely, targeting endogenous Mitostatin by siRNA and anti-sense strategies in PC3 and DU145 prostate cancer cells enhanced the malignant phenotype in both cell lines. In agreement of these anti-oncogenic roles, we discovered that Mitostatin was absent in ∼35% (n = 124) of prostate tumor samples and its overall reduction was associated with advanced cancer stages. Collectively, our findings indicate that MITOSTATIN may acts as a tumor suppressor gene in prostate cancer and provide a novel cellular and molecular mechanism to be further exploited and deciphered in our understanding of prostate cancer progression.
CitationFassan M, D'Arca D, Letko J, Vecchione A, Gardiman MP, McCue P, et al. (2011) Mitostatin Is Down-Regulated in Human Prostate Cancer and Suppresses the Invasive Phenotype of Prostate Cancer Cells. PLoS ONE 6(5): e19771. https://doi.org/10.1371/journal.pone.0019771
Citation to related workPublic Library of Science
Has partPLoS One, Vol. 6, No. 5
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Living with prostate cancer: Randomised controlled trial of a multimodal supportive care intervention for men with prostate cancerChambers, SK; Newton, RU; Girgis, A; Nielsen, L; Lepore, S; Mihalopoulos, C; Gardiner, RA; Galvão, DA; Occhipinti, S; Lepore, Stephen J.|0000-0001-7370-6280 (2011-07-27)Background: Prostate cancer is the most common male cancer in developed countries and diagnosis and treatment carries with it substantial morbidity and related unmet supportive care needs. These difficulties may be amplified by physical inactivity and obesity. We propose to apply a multimodal intervention approach that targets both unmet supportive care needs and physical activity.Methods/design: A two arm randomised controlled trial will compare usual care to a multimodal supportive care intervention "Living with Prostate Cancer" that will combine self-management with tele-based group peer support. A series of previously validated and reliable self-report measures will be administered to men at four time points: baseline/recruitment (when men are approximately 3-6 months post-diagnosis) and at 3, 6, and 12 months after recruitment and intervention commencement. Social constraints, social support, self-efficacy, group cohesion and therapeutic alliance will be included as potential moderators/mediators of intervention effect. Primary outcomes are unmet supportive care needs and physical activity levels. Secondary outcomes are domain-specific and health-related quality of life (QoL); psychological distress; benefit finding; body mass index and waist circumference. Disease variables (e.g. cancer grade, stage) will be assessed through medical and cancer registry records. An economic evaluation will be conducted alongside the randomised trial.Discussion: This study will address a critical but as yet unanswered research question: to identify a population-based way to reduce unmet supportive care needs; promote regular physical activity; and improve disease-specific and health-related QoL for prostate cancer survivors. The study will also determine the cost-effectiveness of the intervention.Trial Registration: ACTRN12611000392965. © 2011 Chambers et al; licensee BioMed Central Ltd.
Evaluation of a Web-based Weight Loss Intervention in Overweight Cancer Survivors Aged 50 and Younger: Web-based Weight Loss in Younger Cancer SurvivorsCenter for Obesity Research and Education (Temple University) (2016-12-19)Purpose: Half of adult cancer survivors under age 50 years are obese. Excess body weight is associated with cancer recurrence, and effective weight loss interventions for younger cancer survivors are needed. Commercially available, online weight loss programmes are readily accessible, but few have been studied in this population. This study employed a single‐arm, pre‐post intervention (baseline‐6 month/baseline‐12 month comparisons) to preliminarily explore feasibility, efficacy and safety of an online, commercially available weight loss programme in breast (n = 30) and testicular (n = 16) cancer survivors under age 50 years. Methods: The intervention included three daily components: exercise, nutritional/behavioural modification strategies and health lessons. Intention‐to‐treat and completers analyses were conducted. Feasibility was measured by participation (number of participants enrolled/number screened), retention (number of participants attending 6/12 month study visit/number of enrolled) and self‐reported adherence rates (average of mean percent adherence to each of the three intervention components). Efficacy was assessed by changes in initial weight (percent weight loss). Safety was assessed by adverse events. Results: The mean participation rate was 42%. The retention rate was 59% at 6 and 49% at 12 months. The adherence rate for all participants (completers/dropouts/lost‐to‐follow‐up) was 50.1% at 6 and 44% at 12 months. Completers reported adherence rates of 68% at 12 months. Study participants lost 5.3% body weight at 12 months; completers lost 9%. Only three unexpected adverse events (unrelated to the intervention) were reported. Conclusion: Clinically significant weight loss was observed, although retention rates were low. Findings generally support preliminary feasibility, efficacy and safety of this online weight loss programme, and future randomized control trials should be explored.
Homeostasis model assessment to detect insulin resistance and identify patients at high risk of breast cancer development: National Cancer Institute of Naples experienceCapasso, I; Esposito, E; Pentimalli, F; Montella, M; Crispo, A; Maurea, N; D'Aiuto, M; Fucito, A; Grimaldi, M; Cavalcanti, E; Esposito, G; Brillante, G; Lodato, S; Pedicini, T; D'Aiuto, G; Ciliberto, G; Giordano, A; Giordano, Antonio|0000-0002-5959-016X (2013-03-18)Background: Metabolic Syndrome (MS) has been correlated to breast carcinogenesis. MS is common in the general population (34%) and increases with age and body mass index. Although the link between obesity, MS and hormone related cancer incidence is now widely recognized, the molecular mechanisms at the basis of such increase are still poorly characterized. A crucial role is supposed to be played by the altered insulin signalling, occurring in obese patients, which fuels cancer cell growth, proliferation and survival. Therefore we focused specifically on insulin resistance to investigate clinically the potential role of insulin in breast carcinogenesis. Methods. 975 patients were enrolled and the association between MS, insulin resistance, and breast cancer was evaluated. Women were stratified by age and menopausal status. Insulin resistance was measured through the Homeostasis Model Assessment score (HOMA-IR). The cut off value to define insulin resistance was HOMA-IR ≥ 2.50. Results: Higher prevalence of MS (35%) was found among postmenopausal women with breast cancer compared to postmenopausal healthy women (19%) [OR 2.16]. A broad range of BMI spanning 19-48 Kg/m§ssup§2§esup§ was calculated. Both cases and controls were characterized by BMI ≥ 25 Kg/m§ssup§2§esup§ (58% of cases compared to 61% of controls). Waist circumference >88 cm was measured in 53% of cases - OR 1.58- (95% CI 0.8-2.8) and in 46% of controls. Hyperinsulinemia was detected in 7% of cases - OR 2.14 (95% CI 1.78-2.99) and only in 3% of controls. HOMA-IR score was elevated in 49% of cases compared to 34% of controls [OR 1.86], suggesting that insulin resistance can nearly double the risk of breast cancer development. Interestingly 61% of women operated for breast cancer (cases) with HOMA-IR ≥ 2.5 presented subclinical insulin resistance with fasting plasma glucose levels and fasting plasma insulin levels in the normal range. Both android fat distribution and insulin resistance correlated to MS in the subgroup of postmenopausal women affected by breast cancer. Conclusions: Our results further support the hypothesis that MS, in particular insulin resistance and abdominal fat, can be considered as risk factors for developing breast cancer after menopause. We suggest that HOMA-IR, rather than fasting plasma glucose and fasting plasma insulin levels alone, could be a valuable tool to identify patients with subclinical insulin resistance, which could be relevant for primary prevention and for high risk patient screening. © 2013 Capasso et al.; licensee BioMed Central Ltd.