Muñoz, A., Eldridge, W. J., Jakobsen, N. M., Sørensen, H., Wax, A., & Costa, M. (2018). Cellular shear stiffness reflects progression of arsenic-induced transformation during G1. Carcinogenesis. https://doi.org/10.1093/carcin/bgx116
Muñoz A, Eldridge WJ, Jakobsen NM, Sørensen H, Wax A, Costa M. Cellular shear stiffness reflects progression of arsenic-induced transformation during G1. Carcinogenesis. 2018. doi:10.1093/carcin/bgx116
Muñoz, A., et al. "Cellular shear stiffness reflects progression of arsenic-induced transformation during G1." Carcinogenesis, 2018.
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RRM Academy Synopsis
Arsenic-exposed bronchial cells had lower stiffness than controls
A cell-culture study of human bronchial cells found that cells exposed to arsenic were softer than unexposed control cells. Clonal lines selected for growth in soft agar showed the same direction: arsenic clones were softer than control clones and varied less in stiffness.
Study at a glance, laboratory experiment of human bronchial cells: Arsenic-exposed bronchial cells were softer than controls. Source: Muñoz A et al., 2018, PMID 29069374.
Key Findings
Median stiffness was lower after 4 weeks (n = 53, P = 0.03) and 12 weeks (n = 73, P < 0.001) of arsenic exposure than in controls (n = 67).
The arsenic-exposed population formed 36, 52 and 35 soft-agar colonies per well against 3, 3 and 2 for controls, a factor 15 increase the authors read as transformation.
Arsenic clones (n = 286) had lower median stiffness than control clones (n = 224; P < 0.001) and a lower model-based relative standard deviation (0.55 against 0.71; P = 0.003).
Arsenic clones had a lower relative standard deviation than their Arsenic 4w parent population (P = 0.003), while control clones showed no significant reduction from their parent population (P = 0.54).
A549 lung cancer cells (n = 60) had a median stiffness within the range of the arsenic-treated populations and the lowest relative standard deviation of any population, 0.47.
Interpretation
The study is a laboratory experiment on cultured human bronchial epithelial cells. Stiffness was measured only in G1, the growth phase before DNA copying, and compared across whole populations. The authors intend the cultures to serve as a proxy for cancer development in the body. They state that developing stiffness as a biomarker would require study in situ, meaning in the body, and a suitable reference distribution, which may vary with cell type and age. In this model, the arsenic clones, which represent a later stage of transformation, showed further reduced stiffness and a narrower spread of stiffness values.
RRM Context
Restorative reproductive medicine looks for root causes, and environmental exposure is part of that search. The authors describe arsenic as a carcinogen known to promote cancers that include bladder, lung and prostate cancers. The paper adds basic-science evidence on how cell stiffness changes over weeks of exposure to this carcinogen.
Our editorial summary of this paper, not the article's abstract.
Abstract
Cancer cells consistently exhibit decreased stiffness; however, the onset and progression of this change have not been characterized. To study the development of cell stiffness changes, we evaluated the shear stiffness of populations of cells during transformation to a carcinogenic state. Bronchial epithelial cells were exposed to sodium arsenite to initiate early stages of transformation. Exposed cells were cultured in soft agar to further transformation and select for clonal populations exhibiting anchorage-independent growth. Shear stiffness of various cell populations in G1 was assessed using a novel non-invasive assay that applies shear stress with fluid flow and evaluates nanoscale deformation using quantitative phase imaging (QPI). Arsenic-treated cells exhibited reduced stiffness relative to control cells, while arsenic clonal lines, selected by growth in soft agar, were found to have reduced stiffness relative to control clonal lines, which were cultured in soft agar but did not receive arsenic treatment. The relative standard deviation (RSD) of the stiffness of Arsenic clones was reduced compared with control clones, as well as to the arsenic-exposed cell population. Cell stiffness at the population level exhibits potential to be a novel and sensitive framework for identifying the development of cancerous cells.
