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Titolo:
IN-VITRO MODULATION OF TUMOR PROGRESSION-ASSOCIATED PROPERTIES OF HORMONE-REFRACTORY PROSTATE CARCINOMA CELL-LINES BY CYTOKINES
Autore:
SOKOLOFF MH; TSO CL; KABOO R; TANEJA S; PANG S; DEKERNION JB; BELLDEGRUN AS;
Indirizzi:
UNIV CALIF LOS ANGELES,SCH MED,DEPT SURG,DIV UROL,PROSTATE CANC PROGRAM,IMMUNOTHERAPY LAB LOS ANGELES CA 90024 UNIV CALIF LOS ANGELES,SCH MED,DEPT SURG,DIV UROL,PROSTATE CANC PROGRAM,IMMUNOTHERAPY LAB LOS ANGELES CA 90024 UNIV CALIF LOS ANGELES,SCH MED,JONSSON COMPREHENS CANC CTR LOS ANGELES CA 00000
Titolo Testata:
Cancer
fascicolo: 9, volume: 77, anno: 1996,
pagine: 1862 - 1872
SICI:
0008-543X(1996)77:9<1862:IMOTPP>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
INTERCELLULAR-ADHESION MOLECULE-1; NECROSIS FACTOR-ALPHA; E-CADHERIN; CANCER; EXPRESSION; GENE; METASTASIS; MELANOMA; ANTIGEN; LYMPHOCYTES;
Keywords:
CYTOKINES; PROSTATE CANCER; PROSTATE-SPECIFIC ANTIGEN; CELL ADHESION MOLECULES; IMMUNOTHERAPY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
49
Recensione:
Indirizzi per estratti:
Citazione:
M.H. Sokoloff et al., "IN-VITRO MODULATION OF TUMOR PROGRESSION-ASSOCIATED PROPERTIES OF HORMONE-REFRACTORY PROSTATE CARCINOMA CELL-LINES BY CYTOKINES", Cancer, 77(9), 1996, pp. 1862-1872

Abstract

BACKGROUND, Cytokines exert cytostatic and immunomodulatory effects on carcinoma cells. Growth inhibition of human prostate carcinoma by cytokines has been demonstrated both in vitro and in vivo, whereas the cellular and molecular changes in prostate carcinoma properties after cytokine treatment have never been characterized. We have thus investigated whether the intrinsic properties of prostate carcinoma cells thatare associated with tumor development and progression can be altered by direct cytokine treatment. METHODS, LNCaP, DU-145, and PC-3 cell lines were treated with tumor necrosis factor-alpha (TNF-alpha) (200 U/mL), interferon-gamma (IFN-gamma) (500 U/mL), human leukocyte interferon (IFN-alpha) (500 U/mL), and interleukin-2 (IL-2) (400 U/mL). The expression of (prostate-specific antigen [PSA] and prostate-specific membrane [PSM]), androgen receptor (AR), growth factors, oncogenes, collagenase, cell adhesion molecules, HLA, antigens, cell adhesion to human bone marrow stroma, and cell growth were determined by quantitative polymerase chain reaction (PCR) analysis, fluorescence-activated cell sorter (FACS) analysis, and cell attachment and proliferation assays, and were compared with nontreated cells. RESULTS, PCR analysis indicatedthat only LNCaP cells expressed PSA, PSM, and AR mRNA. Cytokine treatment did not alter PSM mRNA expression, whereas a 15-fold decrease in PSA and a 5-fold reduction in AR mRNA expression was detected in TNF-cu-treated cells. The down regulation of PSA production was also demonstrated at the protein level in a dose-dependent fashion. A fivefold decrease in PSA mRNA expression was also detected in IL-2-treated LNCaP cells but without a reduction in AR. Down regulated epidermal growth factor receptor (EGF-R) and basic fibroblast growth factor (b-FGF) mRNAexpressions were detected in TNF-alpha- and IFN-alpha-treated DU-145 and PC-3 cells, whereas, only reduced EGF-R expression was observed inLNCaP cells. lFN-gamma and IL-2 treatment down regulated the expression of collagenase Type IV mRNA in DU-145 and PC-3 cells, whereas tumortransforming growth factor-beta (TGF-beta) and IL-6 mRNA expressions did not exhibit any essential changes after cytokine treatment. A reduction in c-myc mRNA expression was observed in TNF-alpha- and IFN-alpha-treated cells, whereas no change in HER-2 expression was noted in any cytokine treated cells. Up regulated P-cadherin, but not E-cadherin,mRNA expression was detected in TNF-alpha- and IFN-gamma-treated PC-3cells. FAGS analysis revealed that all but IL-2-treated cells had enhanced HLA Class I expression, with the maximum effect seen in TNF-alpha-treated LNCaP cells (threefold increase). Up regulated HLA Class II expression was seen only in IFN-gamma-treated cells. All cytokine-treated DU-145 and PC-3 cells expressed reduced levels of alpha 3, but notbeta 1, integrin. Up regulation of ICAM-1 expression was seen in all cytokine treated DU-145 and PC-3 cells, whereas no change in CD44 occurred. Cytokine treatment reduced the binding affinity of LNCaP and DU-145, but not of PC-3 cells, to human bone marrow stromal cells, and all cytokines but IL-2 showed a mild to moderate growth inhibition to prostate cancer cells, with a marked inhibition only observed in TNF-alpha-treated LNCaP cells. CONCLUSIONS. Cytokine treatment can effectively alter several prostate carcinoma properties that are closely associated with tumor invasion and a metastatic phenotype, suggesting that immunotherapy via the local delivery of cytokines may have a potentiallytherapeutic role in the treatment of hormone-refractory prostate cancer through both direct and indirect antitumor mechanisms.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/12/20 alle ore 04:33:47