D'Esposito, Vittoria (2009) Control of breast cancer cell growth by adipocyte-released factors. [Tesi di dottorato] (Unpublished)


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Item Type: Tesi di dottorato
Resource language: English
Title: Control of breast cancer cell growth by adipocyte-released factors
D'Esposito, Vittoriavdesposito@hotmail.it
Date: 30 November 2009
Number of Pages: 69
Institution: Università degli Studi di Napoli Federico II
Department: Biologia e patologia cellullare e molecolare "L. Califano"
Scuola di dottorato: Medicina molecolare
Dottorato: Oncologia ed endocrinologia molecolare
Ciclo di dottorato: 22
Coordinatore del Corso di dottorato:
Vecchio, GiancarloUNSPECIFIED
Formisano, Pietrofpietro@unina.it
Date: 30 November 2009
Number of Pages: 69
Keywords: Adipocyte, breast cancer
Settori scientifico-disciplinari del MIUR: Area 06 - Scienze mediche > MED/05 - Patologia clinica
Date Deposited: 27 May 2010 14:42
Last Modified: 30 Apr 2014 19:39
URI: http://www.fedoa.unina.it/id/eprint/3941
DOI: 10.6092/UNINA/FEDOA/3941

Collection description

Obesity is one of the most challenging and growing health problems, worldwide. Epidemiologic studies now provide compelling evidence that obesity is a risk factor for both cancer incidence and mortality. In particular, obesity increases rates of breast cancer in postmenopausal women and is associated with poorer survival and increased recurrence of disease, regardless the menopausal status. It is now becoming clear that adipocytes, which represent very abundant cell types surrounding cancer cells, particularly in the mammary gland, could influence several aspects of tumorigenesis, from promoting local invasion to angiogenesis and metastasis. However, the molecular mechanisms involved in the adipocyte control of the malignant phenotype remain poorly understood. I have studied the mechanisms by which adipocytes may integrate metabolic and nutritional inputs and produce signals affecting breast cancer cell phenotypes. I have obtained evidence that conditioned media from 3T3-L1 cells induce growth of MCF7 cells, in a time-dependent manner. In particular, conditioned media from fully differentiated adipocytes are 2-fold more effective than conditioned media from pre-adipocytes in inducing MCF7 growth. Cell cycle analysis by flow cytometry revealed that these changes are due to reduced apoptosis instead of increased proliferation. Pre-incubation with low glucose medium or insulin reduces the effect of adipocyte conditioned media on MCF7 growth. Cytokines/growth factors screening of conditioned media from pre-adipoctyte and adipocyte, cultured in presence or in absence of low glucose medium or insulin, revealed that KC, RANTES and IGF1 could be good candidates in mediating pro-tumorigenic effect of adipocyte conditioned media. Moreover, IGF1R inhibitor AG1024 is able to revert adipocyte conditioned media effect. In conclusion, adipocyte-derived factors promote breast cancer cell growth inhibiting the apoptosis. This effect is more evident in adipocytes than in pre-adipocytes and is altered by insulin or nutritional factors such as glucose. The effects are likely mediated by IGF-1.


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