Impedimetric detection of mutant p53 biomarker-driven metastatic breast cancers under hyposmotic pressure.

Menglu Shi,Jill Bargonetti,Alla Polotskaia,Nataly Shtraizent,Hiroshi Matsui,Chunhong Yan

doi:10.1371/journal.pone.0099351

Menglu Shi, Jill Bargonetti + Show 4 more

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https://doi.org/10.1371/journal.pone.0099351

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Abstract

In cancer cells, the oncogenic mutant p53 (mtp53) protein is present at high levels and gain-of-function (GOF) activities with more expression of mtp53 proteins contribute to tumor growth and metastasis. Robust analytical approaches that probe the degree of metastasis of cancer cells in connection with the mtp53 activity will be extremely useful not only for establishing a better cancer prognosis but also understanding the fundamental mechanism of mtp53 oncogenic action. Here we assessed the influence of mtp53 in breast cancers to the mechanical property of breast cancer cells. Recently, ovarian and kidney cancer cell lines have been shown to have higher cellular elasticity as compared to normal cells assessed by monitoring the degree of deformation under hyposmotic pressure. To make fast detection in large scale, the impedance measurement was applied to monitor the swelling ratio of cells with time. The results showed that knockdown of mtp53 leads to decrease in cell swelling. In addition, by means of two types of impedimetric detection systems we consistently detected enhancement of impedance signal in mtp53-expressing breast cancer cells. Based on this observation we hypothesize that highly expressed mtp53 in metastatic mutant breast cancers can promote tumor progression by making cells more deformable and easier to spread out through extracellular matrix. The identification via the electric measurement can be accomplished within 10 minutes. All results in this report suggest that electric probing for the extent of the mtp53 expression of breast cancer cells may serve as a meaningful fingerprint for the cancer diagnostics, and this outcome will also have an important clinical implication for the development of mtp53-based targeting for tumor detection and treatment.

Highlights

Constant efforts are being made to improve diagnostics and treatment of breast cancer, justified by the fact that certain subtypes of breast cancer do not respond to existing endocrine therapy
Wild-type p53 is present at low levels due to fast turn over, and its stabilization is triggered by DNA damage followed by activation of signaling cascades that result in either DNA repair or apoptosis
Discovery of a novel approach that provides an assessment of metastatic potential of cancer cells in connection with the p53 activity, will be useful for establishing a more accurate cancer prognosis and understanding the fundamental mechanism of mtp53 oncogenic action

Summary

Introduction

Constant efforts are being made to improve diagnostics and treatment of breast cancer, justified by the fact that certain subtypes of breast cancer do not respond to existing endocrine therapy. In this respect identification of novel biomarkers and their implication in diagnostics and targeted therapy remains a high priority. Cancer cells express mtp proteins with a range of gain-of-function (GOF) activities, contributing to tumor growth and metastasis [5–8]. In agreement with this hypothesis, mice with mutant p53 developed a broad spectrum of tumors as compared to p53 knockout mice [9,10]. Discovery of a novel approach that provides an assessment of metastatic potential of cancer cells in connection with the p53 activity, will be useful for establishing a more accurate cancer prognosis and understanding the fundamental mechanism of mtp oncogenic action

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