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Optimum Serum Concentration Enhances Migration of MDA-MB-231 Triple-Negative Breast Cancer Cells and Promotes
Yurina Araki1, Tomoka Takatani-Nakase2, Sohei Ninomiya1
1Department of Biological Chemistry, Graduate School of Science, Osaka Metropolitan University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan.
Abstract:
Breast cancer remains one of the most prevalent cancers among women, with triple-negative breast cancer (TNBC), lacking estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2, accounting for approximately 15-20% of all patients with breast cancer. TNBC is notably aggressive, with a high invasive, metastatic, and recurrence potential. In this study, we found that the migration and invasion capabilities of MDA-MB-231 cells, derived from human TNBC, were strongly influenced by the serum concentration. Transwell assays revealed that TNBC cell migration varied depending on the fetal bovine serum (FBS) level, with an optimal concentration that substantially enhanced migration and invasion. In contrast, non-TNBC MCF-7 cells exhibited no such serum-dependent migration pattern. In addition to data-independent acquisition (DIA) phosphoproteomic analysis for understanding the mechanisms, the cellular uptake of the flock house virus coat (35-49) peptide, a type of arginine-rich cell-penetrating peptide with serum-dependent cellular uptake efficacy, was significantly increased under the optimal serum conditions, which induces cell migration, leading to efficient delivery of apoptosis-inducible peptide and TNBC-killing activity. Our findings highlight the critical role of serum concentration in regulating TNBC behavior and offer insights into leveraging serum-responsive delivery systems for targeted breast cancer therapy.
Insights
Serum concentration significantly impacts triple-negative breast cancer (TNBC) cell migration and invasion. Optimal serum levels enhance TNBC cell uptake of therapeutic peptides, offering new targeted therapy strategies.
Area of Science:
- Oncology
- Cell Biology
- Biochemistry
Background:
- Triple-negative breast cancer (TNBC) is an aggressive subtype lacking key therapeutic targets.
- TNBC exhibits high rates of invasion, metastasis, and recurrence.
- Understanding TNBC cell behavior regulation is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the influence of serum concentration on TNBC cell migration and invasion.
- To elucidate the mechanisms underlying serum-dependent TNBC cell behavior.
- To explore the potential of serum-responsive delivery systems for TNBC therapy.
Main Methods:
- Utilized Transwell assays to assess TNBC cell migration and invasion.
- Analyzed serum concentration effects using MDA-MB-231 (TNBC) and MCF-7 (non-TNBC) cells.
- Employed data-independent acquisition (DIA) phosphoproteomics for mechanistic insights.
- Evaluated cellular uptake and efficacy of a cell-penetrating peptide (Flock House Virus CP (35-49)).
Main Results:
- TNBC cell migration and invasion were significantly enhanced at an optimal fetal bovine serum (FBS) concentration.
- Non-TNBC MCF-7 cells did not exhibit serum-dependent migration patterns.
- Optimal serum conditions increased the uptake of an arginine-rich cell-penetrating peptide.
- Enhanced peptide uptake led to efficient delivery of apoptosis-inducible agents and TNBC cell killing.
Conclusions:
- Serum concentration plays a critical role in modulating TNBC cell aggressiveness.
- Optimal serum conditions facilitate the delivery of therapeutic payloads via cell-penetrating peptides.
- Findings suggest potential for serum-responsive drug delivery systems in targeted TNBC therapy.
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