Macrophages enhance 3D invasion in a breast cancer cell line by induction of tumor cell tunneling nanotubes.
Cancer Rep (Hoboken)
; 2(6): e1213, 2019 12.
Article
en En
| MEDLINE
| ID: mdl-32467880
Background: Metastasis is the cause of most cancer-related deaths. It is known that breast cancer cells in proximity to macrophages become more invasive in an Epidermal Growth Factor (EGF) dependent manner. Tunneling nanotubes (TNTs) are thin, F-actin containing, cellular protrusions that mediate intercellular communication and have been identified in many tumors. The mechanism of TNT formation varies between different cell types. M-Sec (TNFAIP2) has been demonstrated to be involved in TNT formation in some cell types including macrophages. Yet, the requirement of M-Sec in tumor cell TNT formation in response to macrophages has not been explored. Aim: The aim of this study was to determine whether EGF was required for macrophage induced tumor cell TNTs in an M-Sec dependent manner and what possible roles tumor cell TNTs play in tumor cell migration and invasion. Methods and Results: Macrophage Conditioned Media (CM) was used to induce an increase in TNTs in a number of breast cancer cell lines as measured by live cell microscopy. Tumor cell TNT formation by CM was dependent on the presence of EGF which was sufficient to induce TNT formation. CM treatment enhanced the level of M-Sec identified using western blot analysis. Reduction of endogenous M-Sec levels via shRNA in MTLn3 mammary adenocarcinoma cells inhibited the formation of TNTs. The role of tumor cell TNTs in cell behavior was tested using in vitro transwell and 3D invasion assays. No effect on chemotaxis was detected but 3D invasion was reduced following the knockdown of M-Sec in tumor cell TNTs. Conclusions: Our results show that EGF was necessary and sufficient for tumor cell TNT formation which was dependent on cellular M-Sec levels. While tumor cell TNTs may not play a role in individual cell behaviors like chemotaxis, they may be important in more complex tumor cell behaviors such as 3D invasion.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Citoesqueleto de Actina
/
Neoplasias de la Mama
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Macrófagos
/
Microtúbulos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Cancer Rep (Hoboken)
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos