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Nuclear Stiffening Inhibits Migration of Invasive Melanoma Cells

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Abstract

During metastasis, melanoma cells must be sufficiently deformable to squeeze through extracellular barriers with small pore sizes. We visualize and quantify deformability of single cells using micropipette aspiration and examine the migration potential of a population of melanoma cells using a flow migration apparatus. We artificially stiffen the nucleus with recombinant overexpression of Δ50 lamin A, which is found in patients with Hutchison Gilford progeria syndrome and in aged individuals. Melanoma cells, both WM35 and Lu1205, both show reduced nuclear deformability and reduced cell invasion with the expression of Δ50 lamin A. These studies suggest that cellular aging including expression of Δ50 lamin A and nuclear stiffening may reduce the potential for metastatic cancer migration. Thus, the pathway of cancer metastasis may be kept in check by mechanical factors in addition to known chemical pathway regulation.

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Acknowledgments

We kindly acknowledge funding from the NIH (CA-125707 to CD) and NSF (CBET 0954421 CAREER to KND).

Ethical Standards

No human or animal studies were carried out by the authors for this article.

Conflicts of interest

A.J.S.R., P.K., A.S., C.D. and K.N.D. declare they have no conflicts of interest.

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Authors and Affiliations

  1. Department of Biomedical Engineering, Carnegie Melon University, Pittsburgh, PA, 15213, USA

    Alexandre J. S. Ribeiro, Aishwarya Sukumar & Kris Noel Dahl

  2. Department of Bioengineering, The Pennsylvania State University, University Park, PA, 16802, USA

    Payal Khanna & Cheng Dong

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  1. Alexandre J. S. Ribeiro
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  2. Payal Khanna
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  3. Aishwarya Sukumar
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  4. Cheng Dong
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  5. Kris Noel Dahl
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Correspondence to Kris Noel Dahl.

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Associate Editor Michael R. King oversaw the review of this article.

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Ribeiro, A.J.S., Khanna, P., Sukumar, A. et al. Nuclear Stiffening Inhibits Migration of Invasive Melanoma Cells. Cel. Mol. Bioeng. 7, 544–551 (2014). https://doi.org/10.1007/s12195-014-0358-3

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