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Chemotaxis Model for Breast Cancer Cells Based on Signal/Noise Ratio.

ABSTRACT: Chemotaxis, a biased migration of cells under a chemical gradient, plays a significant role in diverse biological phenomena including cancer metastasis. Stromal cells release signaling proteins to induce chemotaxis, which leads to organ-specific metastasis. Epidermal growth factor (EGF) is an example of the chemical attractants, and its gradient stimulates metastasis of breast cancer cells. Hence, the interactions between EGF and breast cancer cells have long been a subject of interest for oncologists and clinicians. However, most current approaches do not systematically separate the effects of gradient and absolute concentration of EGF on chemotaxis of breast cancer cells. In this work, we develop a theoretical model based on signal/noise ratio to represent stochastic properties and report our microfluidic experiments to verify the analytical predictions from the model. The results demonstrate that even under the same EGF concentration gradients (0-50 or 0-150 ng/mL), breast cancer cells reveal a more evident chemotaxis pattern when the absolute EGF concentrations are low. Moreover, we found that reducing the number of EGF receptors (EGFRs) with addition of EGFR antibody (1 ng/mL) can promote chemotaxis at an EGF gradient of 0-1 ng/mL as shown by chemotaxis index (0.121 ± 0.037, reduced EGFRs vs. 0.003 ± 0.041, control). This counterintuitive finding suggests that EGFR-targeted therapy may stimulate metastasis of breast cancer because the partial suppression of the receptors makes the number of receptors close to the optimal one for chemotaxis. This analysis should be considered in anticancer drug design.

SUBMITTER: Lim S

PROVIDER: S-EPMC6303234 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Chemotaxis Model for Breast Cancer Cells Based on Signal/Noise Ratio.

Lim Seongjin S Nam Hyeono H Jeon Jessie S JS

Biophysical journal 20181004 10

Chemotaxis, a biased migration of cells under a chemical gradient, plays a significant role in diverse biological phenomena including cancer metastasis. Stromal cells release signaling proteins to induce chemotaxis, which leads to organ-specific metastasis. Epidermal growth factor (EGF) is an example of the chemical attractants, and its gradient stimulates metastasis of breast cancer cells. Hence, the interactions between EGF and breast cancer cells have long been a subject of interest for oncol ...[more]

PMID: 30366624

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Project description:MotivationTarget-specific hybridization depends on oligo-probe characteristics that improve hybridization specificity and minimize genome-wide cross-hybridization. Interplay between specific hybridization and genome-wide cross-hybridization has been insufficiently studied, despite its crucial role in efficient probe design and in data analysis.ResultsIn this study, we defined hybridization specificity as a ratio between oligo target-specific hybridization and oligo genome-wide cross-hybridization. A microarray database, derived from the Genomic Comparison Hybridization (GCH) experiment and performed using the Affymetrix platform, contains two different types of probes. The first type of oligo-probes does not have a specific target on the genome and their hybridization signals are derived from genome-wide cross-hybridization alone. The second type includes oligonucleotides that have a specific target on the genomic DNA and their signals are derived from specific and cross-hybridization components combined together in a total signal. A comparative analysis of hybridization specificity of oligo-probes, as well as their nucleotide sequences and thermodynamic features was performed on the database. The comparison has revealed that hybridization specificity was negatively affected by low stability of the fully-paired oligo-target duplex, stable probe self-folding, G-rich content, including GGG motifs, low sequence complexity and nucleotide composition symmetry.ConclusionFiltering out the probes with defined 'negative' characteristics significantly increases specific hybridization and dramatically decreasing genome-wide cross-hybridization. Selected oligo-probes have two times higher hybridization specificity on average, compared to the probes that were filtered from the analysis by applying suggested cutoff thresholds to the described parameters. A new approach for efficient oligo-probe design is described in our study.Contactshabalin@ncbi.nlm.nih.gov or olga.matveeva@gmail.comSupplementary informationSupplementary data are available at Bioinformatics online.

Dataset Information

Chemotaxis Model for Breast Cancer Cells Based on Signal/Noise Ratio.

Publications

Chemotaxis Model for Breast Cancer Cells Based on Signal/Noise Ratio.

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