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Effects of nIFN β and rifn γ on growth and morphology of two human melanoma cell lines: Comparison between two‐and three‐dimensional culture
Author(s) -
Görlach A.,
Herter P.,
Hentschel H.,
Frosch P. J.,
Acker H.
Publication year - 1994
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910560218
Subject(s) - spheroid , cell culture , cell growth , biology , recombinant dna , interferon , interferon gamma , cytokine , immunology , andrology , microbiology and biotechnology , medicine , biochemistry , genetics , gene
We compared the anti‐proliferative effects of natural inter‐feron β (nIFN β) and recombinant interferon γ (HFN γ) on 2 human melanoma cell lines, IGRI and SK‐Me128, grown in 2‐dimensional monolayer and in 3‐dimensional spheroid culture. In monolayer culture, growth of both lines was inhibited in a dose‐dependent manner by 5‐day treatments with IFN in concentrations ranging between I and 5,000 IU/ml. Incubations with 120 IU/ml nIFN βor 25 IU/ml rIFN γ led to a 50% growth inhibition of IGRI cells. A 50% growth inhibition of SK‐Me128 cells was obtained with 60 IU/ml nIFN β, whereas even 5,000 IU/ml rIFN γ inhibited the growth of this line by only 30%. Growing these melanoma cell lines in 3‐dimensional spheroid culture for 5 days reduced their sensitivity to interferon. Growth inhibition values of 50% were achieved with 3,000 IU/ml rIFN γ or 9,000 IU/ml nIFN β for IGRI spheroids and 10,000 IU/ml nIFN β for SK‐Me128 spheroids, while 10,000 IU/ml rIFN γ reduced the growth of SK‐Me128 spheroids by only 25%. Outgrowth tests showed that the proliferative capacity after 5‐day incubations with IFN was only reduced in IGRI spheroids treated with high doses of nIFN β. The macroscopically observed increased density of interferon‐treated spheroids could be confirmed by light microscopy as corresponding to reduced intercellular space in these spheroids. Scanning electron microscopy furthermore showed variations on the surface of IFN‐treated spheroids as well as in cellular organization and structures between cells, hinting at a possible involvement of extracellular matrix substances in the reaction to interferons. These findings show that the high anti‐proliferative sensitivity of the melanoma cell lines in monolayer culture could not be achieved in spheroid culture. The volume decreases seen in the presence of interferon might be, at least in part, due to an increased packing density in combination with changes in the cellular organization of interferon‐treated spheroids, rather than to direct antiproliferative effects.