The Presence of Yin-Yang Effects in the Migration Pattern of Staurosporine-Treated Single versus Collective Breast Carcinoma Cells

Abstract

Background: Staurosporine-dependent single and collective cell migration patterns of breast carcinoma cells MDA-MB-231, MCF-7, and SK-BR-3 were analysed to characterise the presence of drug-dependent migration promoting and inhibiting yin-yang effects. Methods: Migration patterns of various breast cancer cells after staurosporine treatment were investigated using Western blot, cell toxicity assays, single and collective cell migration assays, and video time-lapse. Statistical analyses were performed with Kruskal–Wallis and Fligner–Killeen tests. Results: Application of staurosporine induced the migration of single MCF-7 cells but inhibited collective cell migration. With the exception of low-density SK-BR-3 cells, staurosporine induced the generation of immobile flattened giant cells. Video time-lapse analysis revealed that within the borderline of cell collectives, staurosporine reduced the velocity of individual MDA-MB-231 and SK-BR-3, but not of MCF-7 cells. In individual MCF-7 cells, mainly the directionality of migration became disturbed, which led to an increased migration rate parallel to the borderline, and hereby to an inhibition of the migration of the cell collective as a total. Moreover, the application of staurosporine led to a transient activation of ERK1/2 in all cell lines. Conclusion: Dependent on the context (single versus collective cells), a drug may induce opposite effects in the same cell line.

Targeting c-Jun is a potential therapy of luminal breast cancer bone metastasis

“…It should be noticed that the wound-healing assay is used to evaluate collective-cell migration, whereas the trans-well assay is a single-cell migration assay 36,37 . In previous reports, MCF7 exhibited different migration phenotypes under stimulations or genetic mutations; for example, HCLS1-associated protein X-1 knockdown in MCF7 only affected wound-healing migration, not trans-well migration ability 38 , and staurosporine induced migration in single cells but inhibited collective MCF7 cell migration 39 . In the present study, compared with parental cells, MCF7-BM02 cells showed stronger collective-cell migration than single-cell migration ability, which was mediated by c-Jun protein expression.…”

LIM1863 is useful to explore collective cancer cell migration, and the group of heterogeneous cells undergoing collective migration behaves like a supracellular unit

“…Jansson et al (2016) found that about 90% of CTCs were apoptotic (Jansson et al, 2016). This phenomenon is rarely observed in CCCM models in vitro (Saenz-de-Santa-Maria et al, 2020; Meyer et al, 2021;Ogoke et al, 2021). However, in LIM1863, most of the cells undergoing CCCM died.…”

“…CCCM is a highly discussed and very current topic, but it is far from clear. Monolayer cells and spheroids embedded in extracellular matrices are two commonly used in vitro models (Saenz-de-Santa-Maria et al, 2020;Meyer et al, 2021;Ogoke et al, 2021). Monolayer cells cannot well recapitulate threedimensional architecture, for example, intercellular adhesion, of CCCM in vivo.…”

Molecular Research and Treatment of Breast Cancer

“…Another important strategy in drug design is the development of agents capable of inhibiting the metastasis of cancer cells and the evaluation of their activity toward cell migration and invasion. The research of Meyer et al [ 14 ] showed that drugs could elicit a diverse response on the migration of tumor cells, depending on cell–cell and cell–extracellular matrix interactions. Breast cancer cells treated with staurosporine displayed different migratory properties, which were context-dependent, subject to the presence of single or collective cells, and on growth substratum.…”

“…Breast cancer cells treated with staurosporine displayed different migratory properties, which were context-dependent, subject to the presence of single or collective cells, and on growth substratum. Thus, the influence of a drug on the migration of tumor cells can be dependent not only on the cell line type, but also on the particular cellular context, which should be examined in order to fully elucidate the impact profile of a drug [ 14 ].…”