Cancer metastasis is the result of a series of deregulated biologicalphenomena, including alterations of cell-cell and cell-matrixinteractions and of other microenvironmental conditions such asthe oxygen tissue supply. Hypoxia is a well-known driver ofaggressive cancer phenotypes, indeed tumors with poor prognosishave higher proportions of anoxic and hypoxic areas1. Theconsequences of tumour hypoxia can be local or even systemictowards distant organs, and it can evoke diversified responses:whereas low oxygen concentration in tissue environments. (pO2<7 mmHg) exerts anti-proliferative effects and promotes differentiation,apoptosis and/or necrosis on normal cells, thetumoral cells react to hypoxic stress with adaptive processesthat confer them an aggressive phenotype2. Indeed, the hypoxicmicroenvironment in tumors contributes to alter energy metabolism,cell growth and responsiveness to therapy.The aim of present study was the identification, by a proteomicstrategy, of the effects exerted by hypoxic conditions on the8701-BC breast cancer cells compared with HB2 immortalizednormal mammary epithelial cells. For this purpose, the two cellcultures, were grown at low oxygen content (pO2=2%) in parallelwith normoxic cells (pO2=20%).Hypoxic and normoxic cells at confluence were then properlycollected, lysed and subjected to 2D-IPG based proteomicanalysis3. Proteins identified by several methods4 were thenclusterized by using the gene ontology database DAVID. Theresults showed that the hypoxic condition exerts different effectson the proteomic profile of the two cell lines.In particular, a general down-regulation of the proteome complementwas observed for the HB2 cells and especially for theclasses of the negative regulators of apoptosis and of the proteinsinvolved in membrane vesiculation. Conversely, the proteomicprofile of the 8701-BC cells was not altered significantlyby the hypoxia, except for the highly modulated protein class ofthe cytoskeleton.These data suggest that hypoxia may depress cell behaviour ofnon-tumoral cells, while is ineffective on neoplastic cells, basicallyadapted to anaerobic metabolism, or even promotes cellmotility which contributes in directing the tumour cells toacquire a more aggressive phenotype.
|Numero di pagine||1|
|Rivista||EUROPEAN JOURNAL OF HISTOCHEMISTRY|
|Stato di pubblicazione||Published - 2015|
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