Characterizing the malignancy and drug resistance of cancer cells from their membrane resealing response.

T H Hui,T Y Lee,Z L Zhou,Joseph S K Au,Roger K C Ngan,Y Lin,H W Fong,Timothy T C Yip,A H W Ngan

doi:10.1038/srep26692

T H Hui, T Y Lee + Show 7 more

Open Access

https://doi.org/10.1038/srep26692

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Abstract

In this report, we showed that two tumor cell characteristics, namely the malignancy and drug-resistance status can be evaluated by their membrane resealing response. Specifically, membrane pores in a number of pairs of cancer and normal cell lines originated from nasopharynx, lung and intestine were introduced by nano-mechanical puncturing. Interestingly, such nanometer-sized holes in tumor cells can reseal ~2–3 times faster than those in the corresponding normal cells. Furthermore, the membrane resealing time in cancer cell lines exhibiting resistance to several leading chemotherapeutic drugs was also found to be substantially shorter than that in their drug-sensitive counterparts, demonstrating the potential of using this quantity as a novel marker for future cancer diagnosis and drug resistance detection. Finally, a simple model was proposed to explain the observed resealing dynamics of cells which suggested that the distinct response exhibited by normal, tumor and drug resistant cells is likely due to the different tension levels in their lipid membranes, a conclusion that is also supported by direct cortical tension measurement.

Highlights

Membrane pores in the nasopharyngeal carcinoma (NPC) cell line, HONE1 were created by a 500 nm -radius AFM indenter (Fig. 1A)
We found that there is a strong correlation between the resealing response of tumor cells and their capability to resist anti-cancer drugs with a clearly shortened resealing time in different cancer cells with resistance against commonly used drugs including Cisplatin, AUY922 and Erlotinib
Previous studied have found that several cancer cells have a lower cortical tension[11,26] compared to their normal counterparts that possess a better differentiated cytoskeleton[26]

Summary

Introduction

To test whether the membrane resealing time is correlated with the resistance to Erlotinib, we performed the same membrane resealing experiments in nine different well-established lung cancer cell lines (HCC827, NCI-H3255, HCC2935, NCI-H358, NCI-H1650, A549, NCI-H23, NCI-H1975& NCI-H820). Within this theoretical framework, the observed big difference in the resealing time of tumor and normal cells can be well explained by assuming that the tension level in cancer cells is much lower than that in the corresponding normal ones.

Results

Conclusion