Related Experiment Videos
Role of proliferation for intercellular induction of apoptosis
D Bassler1, H D Brauns, G Bauer
1Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Universität Freiburg, Germany.
Abstract:
We have recently described induction of apoptosis of transformed target cells by TGF-beta-treated nontransformed effector cells as a potential novel control step in oncogenesis. Here we study the role of proliferation of both cell types for the efficiency of induction of apoptosis. Inhibition of proliferation of transformed target cells by gamma irradiation or colchicine treatment did not affect their sensitivity to induction of apoptosis by TGF-beta-treated nontransformed effector cells. This finding indicates that sensitivity to intercellular induction of apoptosis is not related to cell cycle control. In contrast, the ability of nontransformed effector cells to induce apoptosis was dependent on their proliferation. Nontransformed cells blocked by gamma irradiation, colchicine treatment, or thymidine treatment were no longer able to induce apoptosis of transformed target cells. This inability seems to be partially due to substances that are released from proliferation-inhibited nontransformed effector cells and that interfere with induction of apoptosis.
Insights
Nontransformed cells require proliferation to induce apoptosis in cancer cells, a process crucial for oncogenesis control. Inhibiting cancer cell proliferation does not affect their sensitivity to this cell-mediated killing.
Area of Science:
- Oncology
- Cell Biology
- Immunology
Background:
- Transforming growth factor-beta (TGF-beta) can induce apoptosis in transformed cells via nontransformed effector cells.
- This intercellular apoptosis induction is a potential mechanism for controlling oncogenesis.
- The role of cell proliferation in this process requires further investigation.
Purpose of the Study:
- To investigate the impact of transformed target cell proliferation on apoptosis induction.
- To determine the influence of nontransformed effector cell proliferation on their ability to induce apoptosis.
- To elucidate the mechanisms underlying effector cell proliferation-dependent apoptosis induction.
Main Methods:
- Inhibition of transformed target cell proliferation using gamma irradiation and colchicine.
- Inhibition of nontransformed effector cell proliferation using gamma irradiation, colchicine, and thymidine.
- Assessment of apoptosis induction in target cells following co-culture with treated effector cells.
Main Results:
- Inhibition of transformed target cell proliferation did not alter their sensitivity to apoptosis induction.
- Proliferation of nontransformed effector cells was essential for their ability to induce apoptosis.
- Proliferation-inhibition of effector cells resulted in the release of substances that interfered with apoptosis induction.
Conclusions:
- Sensitivity to intercellular apoptosis induction is independent of target cell cycle control.
- Nontransformed effector cell proliferation is critical for inducing apoptosis in transformed cells.
- Factors released from proliferation-inhibited effector cells can suppress apoptosis induction, suggesting a regulatory role for effector cell proliferation.