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Cytoskeletal agents inhibit motility and adherence of human tumor cells
M L Stracke1, M Soroush, L A Liotta
1National Institutes of Health, National Cancer Institute, Laboratory of Pathology, Bethesda, Maryland.
Abstract:
Cytoskeletal agents have been demonstrated to inhibit stimulated motility and substrate adherence by the human tumor cell line, A2058. cis-tubulozole, taxol, and cytochalasin D were tested for their effects on chemotaxis in response to a tumor cytokine, autocrine motility factor, and on adherence to several substrata: laminin- and gelatin-coated dishes as well as tissue culture plastic. Cytochalasin D, which inhibits microfilament polymerization, abolished stimulated motility. Taxol, which stabilizes microtubules, decreased stimulated motility to a greater degree than cis-tubulozole, which inhibits microtubular polymerization. In contrast, cis-tubulozole had the greatest inhibitory effect on adherence with a gelatin substratum more affected (100% inhibition) than tissue culture plastic (90%) or laminin substratum (52%). Taxol affected adherence in the same order but less than cis-tubulozole. Cytochalasin D had no significant effect on adherence to laminin with moderate inhibition of adherence to tissue culture plastic or gelatin. These data suggest that, in these tumor cells, microfilaments are more crucial for motility than adherence, but the dynamic polymerization and depolymerization of microtubules are required for both types of cellular activities.
Insights
Cytoskeletal agents like cytochalasin D, taxol, and cis-tubulozole impact tumor cell motility and adherence. Microfilaments are key for motility, while microtubules are crucial for both motility and adherence in A2058 cells.
Area of Science:
- Cell Biology
- Cancer Research
- Biochemistry
Background:
- Cytoskeletal agents modulate cell behavior, including motility and adherence.
- Human tumor cell line A2058 exhibits motility and adherence properties influenced by its microenvironment.
Purpose of the Study:
- To investigate the effects of specific cytoskeletal agents on the chemotaxis and substrate adherence of A2058 human tumor cells.
- To elucidate the distinct roles of microfilaments and microtubules in tumor cell motility and adherence.
Main Methods:
- A2058 cells were treated with cis-tubulozole, taxol, and cytochalasin D.
- Cellular chemotaxis was assessed in response to autocrine motility factor.
- Substrate adherence was measured on laminin-, gelatin-coated, and tissue culture plastic dishes.
Main Results:
- Cytochalasin D (microfilament inhibitor) abolished stimulated motility.
- Taxol (microtubule stabilizer) and cis-tubulozole (microtubule inhibitor) decreased stimulated motility, with taxol being more potent.
- Cis-tubulozole significantly inhibited adherence, particularly to gelatin (100%), followed by tissue culture plastic (90%) and laminin (52%).
- Taxol also inhibited adherence in a similar pattern but to a lesser extent than cis-tubulozole.
- Cytochalasin D had minimal effect on laminin adherence but moderately inhibited adherence to plastic and gelatin.
Conclusions:
- Microfilaments are more critical for A2058 cell motility than for adherence.
- Dynamic polymerization and depolymerization of microtubules are essential for both tumor cell motility and substrate adherence.
- Differential effects of cytoskeletal agents highlight the complex interplay between cytoskeletal components and cancer cell behavior.