title: Effects of TNF-alpha and retinoic acid on the proliferation of the clear cell and chromophilic types of human renal cell carcinoma in vitro.
abstract: Since no effective therapeutic approach is known so far for metastatic renal cell carcinoma (RCC), we analyzed the anti-proliferative effects of TNF-alpha and retinoic acid (RA), applied either alone or in combination on 7 different RCC cell lines in vitro. In 5 out of 7 cell lines, a significant (p < 0.05) dose-dependent inhibition of tumor cell proliferation became evident after exposure to TNF-alpha, the response being of modest magnitude in 5 cell lines. In 2 cell lines the effects were more pronounced with a reduction of cell viability to 55 +/- 11% of the control. Northern blot analysis revealed no expression of TNF-alpha and p75 TNF-receptor in any cell line. All the cell lines showed p55 TNF-receptor mRNA. Scatchard analysis revealed no correlation between TNF-alpha receptor status and growth inhibitory response to TNF-alpha, the number of TNF-receptors per cell ranging from 0 to 3,976, and the affinity values from Kd = 0.621 nmol/l to Kd = 4.28 nmol/l. Exposure to RA alone resulted in significant (p < 0.05), but modest growth inhibition in 2 out of 7 cell lines with a reduction of cell viability to 83 +/- 1% of the control. In 2 out of 7 cell lines, combination of RA and TNF-alpha was significantly (p < 0.05) more effective than the single application of each compound. Northern blot analysis revealed no transcripts of CRABP I and retinoic acid receptor (RAR)-beta. All the cell lines expressed RAR-alpha mRNA and one cell line additionally expressed RAR-gamma mRNA. A correlation between RAR status and RA response was not seen.
authors.affiliation: Institute of Pathology, Heinrich Heine-University, Düsseldorf, Germany.
authors.forename: C D
authors.initials: CD
authors.lastname: Gerharz
authors.forename: U
authors.initials: U
authors.lastname: Ramp
authors.forename: P
authors.initials: P
authors.lastname: Reinecke
authors.forename: U
authors.initials: U
authors.lastname: Ressler
authors.forename: M
authors.initials: M
authors.lastname: Dienst
authors.forename: N
authors.initials: N
authors.lastname: Marx
authors.forename: U
authors.initials: U
authors.lastname: Friebe
authors.forename: R
authors.initials: R
authors.lastname: Engers
authors.forename: K
authors.initials: K
authors.lastname: Pollow
authors.forename: H E
authors.initials: HE
authors.lastname: Gabbert
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000473:pathology*; D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis* / Q000187:drug effects; D015152:Blotting, Northern; D002292:Carcinoma, Renal Cell / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002999:Clone Cells; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000473:pathology*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis* / Q000187:drug effects; D047888:Receptors, Tumor Necrosis Factor, Type I; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D014212:Tretinoin