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Two distinct tumor cell growth-inhibiting factors from a human rhabdomyosarcoma cell line
Abstract:
Tumor cell growth-inhibiting factors (TIFs) have been shown to inhibit the growth of tumor cell lines in culture. TIF-1, the first TIF to be described, is a low-molecular-weight, acid- and heat-stable polypeptide with no antiviral activity. A second class of TIFs (TIF-2) has now been isolated from the conditioned media of a human rhabdomyosarcoma cell line and partially purified by polyacrylamide gel filtration, cation exchange, and reverse-phase high-pressure liquid chromatography. Partially purified preparations of TIF-2 inhibit the growth of a variety of human tumor cells in soft agar and monolayer cultures and are mitogenic for normal human and mouse cells. TIF-2 has no antiviral activity. The growth-inhibitory effects of TIF-2 are reversible when the affected cells are no longer exposed to the factor. Although both TIF-1 and TIF-2 are obtained from the same source, they can be distinguished by their molecular weight, heat lability, elution pattern from reverse-phase high-pressure liquid chromatography, and their effect on the growth of mink lung epithelial cells. The growth of a human tumor cell variant, selected for resistance to growth inhibition by TIF-1, is inhibited by TIF-2. TIFs may therefore be a family of related polypeptides which selectively inhibit the growth of tumor cells.
Insights
Tumor cell growth-inhibiting factors (TIFs) are polypeptides that inhibit tumor cell proliferation. A newly identified TIF-2 selectively inhibits tumor growth and is mitogenic for normal cells, suggesting a family of related factors.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Tumor cell growth-inhibiting factors (TIFs) are known to inhibit tumor cell lines in culture.
- TIF-1, a heat-stable polypeptide, was the first TIF identified.
- TIFs represent a potential class of therapeutic agents targeting tumor cell proliferation.
Purpose of the Study:
- To isolate and characterize a second class of tumor cell growth-inhibiting factors (TIF-2).
- To investigate the biological activities and properties of TIF-2.
- To compare TIF-2 with the previously identified TIF-1.
Main Methods:
- Isolation of TIF-2 from conditioned media of a human rhabdomyosarcoma cell line.
- Partial purification using polyacrylamide gel filtration, cation exchange, and reverse-phase HPLC.
- Assessment of growth inhibition in various human tumor cells and mitogenicity in normal cells.
Main Results:
- TIF-2 was isolated and partially purified, exhibiting selective inhibition of human tumor cell growth in soft agar and monolayer cultures.
- TIF-2 demonstrated mitogenic activity for normal human and mouse cells.
- TIF-2's effects were reversible upon removal of the factor, and it differed from TIF-1 in molecular weight, heat lability, and HPLC elution.
- TIF-2 inhibited a TIF-1-resistant human tumor cell variant.
Conclusions:
- TIF-2 represents a distinct class of tumor cell growth-inhibiting factors with reversible, selective anti-tumor activity.
- TIF-2 is mitogenic for normal cells, suggesting differential effects on cell types.
- TIFs may constitute a family of related polypeptides with potential therapeutic applications in cancer treatment.