title: Transient exposure to cytarabine increases peptide growth factor receptor expression and tumorigenicity of melanoma cells.
abstract: We have demonstrated that anticancer drugs at cytostatic concentrations enhance the expression and function of epidermal growth factor (EGF-R) and transferrin (TRF-R) receptors on human tumor cells. We hypothesized that these effects could represent a protective response of tumor cells to sublethal antiproliferative stimuli which could lead to enhanced growth potential. 72 hours exposure of human melanoma GLL-19 cells to 1,000 nM ara-C induced growth inhibition and increased the number of EGF-R, TRF-R and nerve growth factor receptor (NGF-R) on cell surface. Enhanced expression of beta 3 integrins CD49a, CD49c and CD49e, av integrin CD51, beta 3 integrin CD61, CD58/LFA3 and collagen IV and laminin was also detected in ara-C-treated GLL-19 cells. These changes at the tumor cell surface were paralleled by increased in vitro adhesion, invasive potential and clonogenic growth in soft agar and in vivo tumor formation. A more aggressive tumor cell phenotype is induced in human melanoma cells after transient exposure to cytostatic concentrations of ara-C.
authors.affiliation: Cattedra di Oncologia Medica, Università Federico II di Napoli, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Caraglia
authors.forename: A I
authors.initials: AI
authors.lastname: Leardi
authors.forename: S
authors.initials: S
authors.lastname: Improta
authors.forename: V
authors.initials: V
authors.lastname: Perin
authors.forename: B
authors.initials: B
authors.lastname: Ricciardi
authors.forename: C
authors.initials: C
authors.lastname: Arra
authors.forename: P
authors.initials: P
authors.lastname: Ferraro
authors.forename: A
authors.initials: A
authors.lastname: Fabbrocini
authors.forename: A
authors.initials: A
authors.lastname: Pinto
authors.forename: A R
authors.initials: AR
authors.lastname: Bianco
authors.forename: P
authors.initials: P
authors.lastname: Tagliaferri
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003561:Cytarabine / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D008545:Melanoma / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009374:Neoplasms, Experimental / Q000473:pathology; D009414:Nerve Growth Factors / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D011990:Receptors, Transferrin / Q000378:metabolism*; D014168:Transferrin / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016023:Integrins; D009414:Nerve Growth Factors; D017475:Receptors, Nerve Growth Factor; D011990:Receptors, Transferrin; D014168:Transferrin; D003561:Cytarabine; D004815:Epidermal Growth Factor; D066246:ErbB Receptors