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Effects of anticancer agents on the shedding of cells from human multicellular tumor spheroids
N Kohno1, T Ohnuma, J F Holland
1Department of Neoplastic Diseases, Mount Sinai School of Medicine, New York, N.Y.
Abstract:
We studied the effects of anticancer agents on the inhibition of cell shedding from the surface of multicellular tumor spheroids (MTS). MTS were produced from 2 human tumor cell lines; one melanoma and the other squamous cell lung cancer, by using liquid overlay culture technique. The cell shedding from the melanoma MTS was approximately 10-fold higher than the squamous cell carcinoma MTS. In the melanoma MTS, all 3 drugs studied - vincristine (VCR), doxorubicin (ADR) and cisplatin (DDP)-inhibited cell shedding and the degree of inhibition of cell shedding was drug concentration related. In the squamous cell carcinoma MTS, VCR was as active in inhibiting cell shedding as in the melanoma MTS, but ADR and DDP were less efficacious. When effects on cell shedding were compared with those on cell lethality, VCR produced inhibition of cell shedding at much lower concentrations than those producing cell kill effects. ADR and DDP produced cell lethality as effective as, or more effective than, inhibition of cell shedding. These data seem to parallel known effects of these agents on cell kill and inhibition of metastases. MTS may serve as an in vitro model for the study of cell shedding and metastasis.
Insights
Anticancer drugs effectively inhibit tumor cell shedding from multicellular tumor spheroids (MTS). Vincristine showed potent inhibition at lower concentrations than cell kill, suggesting potential for metastasis prevention.
Area of Science:
- Oncology
- Cell Biology
- Pharmacology
Background:
- Multicellular tumor spheroids (MTS) are used to model tumor behavior.
- Cell shedding from MTS is a potential indicator of metastatic potential.
Purpose of the Study:
- To investigate the effects of anticancer agents on cell shedding from MTS.
- To compare the efficacy of different drugs in inhibiting cell shedding versus causing cell lethality.
Main Methods:
- Generated MTS from human melanoma and squamous cell lung cancer lines using liquid overlay culture.
- Administered vincristine (VCR), doxorubicin (ADR), and cisplatin (DDP) to MTS.
- Quantified cell shedding and cell lethality in response to drug treatment.
Main Results:
- Melanoma MTS exhibited 10-fold higher cell shedding than squamous cell carcinoma MTS.
- VCR, ADR, and DDP inhibited cell shedding from melanoma MTS in a dose-dependent manner.
- VCR inhibited cell shedding effectively in both cell lines; ADR and DDP were less effective in squamous cell carcinoma MTS.
- VCR inhibited cell shedding at lower concentrations than required for cell kill.
- ADR and DDP showed comparable or greater efficacy in cell lethality versus cell shedding inhibition.
Conclusions:
- MTS serve as a valuable in vitro model for studying cell shedding and metastasis.
- Drug-induced inhibition of cell shedding may correlate with reduced metastatic potential.
- Differential drug responses highlight the importance of agent selection for targeting metastasis.