Cellular morphological features are predictive markers of cancer cell state

Alizadeh, Elaheh; Castle, Jordan; Quirk, Analia; Taylor, Cameron D.L.; Xu, Wenlong; Prasad, Ashok

doi:10.1016/j.compbiomed.2020.104044

Cited by 36 publications

(28 citation statements)

References 42 publications

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“…In addition to the presented experimental data, an assessment of β-HCH’s capability to modulate cellular structural plasticity could provide a further element to confirm its carcinogenic potential. Cytoskeletal organization can, in fact, adapt in response to oncogenic stimuli, determining a change in cellular morphology that is aimed at fostering proliferation activity and invasiveness [ 28 ].…”

Section: Resultsmentioning

confidence: 99%

β-Hexachlorocyclohexane Drives Carcinogenesis in the Human Normal Bronchial Epithelium Cell Line BEAS-2B

Rubini

Minacori

Paglia

et al. 2021

IJMS

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Organochlorine pesticides constitute the majority of the total environmental pollutants, and a wide range of compounds have been found to be carcinogenic to humans. Among all, growing interest has been focused on β-hexachlorocyclohexane (β-HCH), virtually the most hazardous and, at the same time, the most poorly investigated member of the hexachlorocyclohexane family. Considering the multifaceted biochemical activities of β-HCH, already established in our previous studies, the aim of this work is to assess whether β-HCH could also trigger cellular malignant transformation toward cancer development. For this purpose, experiments were performed on the human normal bronchial epithelium cell line BEAS-2B exposed to 10 µM β-HCH. The obtained results strongly support the carcinogenic potential of β-HCH, which is achieved through both non-genotoxic (activation of oncogenic signaling pathways and proliferative activity) and indirect genotoxic (ROS production and DNA damage) mechanisms that significantly affect cellular macroscopic characteristics and functions such as cell morphology, cell cycle profile, and apoptosis. Taking all these elements into account, the presented study provides important elements to further characterize β-HCH, which appears to be a full-fledged carcinogenic agent.

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Section: Resultsmentioning

confidence: 99%

β-Hexachlorocyclohexane Drives Carcinogenesis in the Human Normal Bronchial Epithelium Cell Line BEAS-2B

Rubini

Minacori

Paglia

et al. 2021

IJMS

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“…While this work represents a significant advance in characterizing cell adaptation to tissue microenvironments, several limitations of the current approach must be considered. First, while morphology serves as a powerful functional output for cell state, it is a conglomerate of many mechanical [18, 61, 62], biochemical [13, 14], and stochastic [63] processes and therefore cannot inform on the specific pathways regulating cell behaviors such as plasticity. For a deeper understanding of the observed tissue-dependent cell differences we will now have to introduce molecularly-specific probes.…”

Section: Discussionmentioning

confidence: 99%

“…While this work represents a significant advancement in characterization of cell adaptation as a function of tissue microenvironments, several limitations of the current approach must be considered. First, while morphology serves as a powerful functional output for cell state, it is by nature a conglomerate of many mechanical [18,65,66], biochemical [13,14], and cell-intrinsic [11,67] cues and therefore cannot inform on the specific biochemical pathways regulating signaling. Therefore, correlating specific morphological states to organization of mechanical and biochemical signaling pathways at single-cell resolution will allow triangulation of cell states for a deeper understanding of tissue-dependent cell differences.…”

Section: Limitations and Future Prospectsmentioning

confidence: 99%

In vivo profiling of site-specific human cancer cell states in zebrafish

Segal

Mazloom-Farsibaf

Chang

et al. 2021

Preprint

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A key challenge in cancer research is to identify functional cell states as they relate to specific tissue microenvironments. In this work, we present a quantitative high-resolution imaging assay of cancer cell morphology in zebrafish xenografts to probe functional adaptation to variable cell extrinsic cues and molecular interventions. We focus on Ewing Sarcoma, a pediatric cancer driven by a single oncogenic fusion protein EWSR1-FLI1, and with little to no additional somatic mutations, making it a prototypical form of cancer whose adaptation is likely driven by acute, non-genomic mechanisms. By applying machine learning approaches to 3D cell shapes, we find systematic shifts in the distribution of cell morphological states between seeding sites in the fish embryo, as well as between cells with differential expression of EWSR1-FLI1 in an environmentally sensitive fashion. We propose a model where Ewing Sarcoma cancer cell plasticity is sensitive both to expression fluctuation of EWSR1-FLI1 and signals from the surrounding tissue microenvironment, with either or both factors possibly contributing to metastatic potential.

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“…The accurate and sensitive diagnosis of pathologies is an essential determinant of patient treatment outcome and prognosis. Given that cell morphology, structure, and chemical composition are linked to physiological function, they can be used as essential markers for diagnosis ( Alizadeh et al., 2020 ). Among such markers, morphology is still the most important criterion for diagnosis and also constitutes a more resource-effective alternative to molecular diagnosis approaches if two conditions are met: (1) morphological patterns are available for accurate and sensitive diagnosis and (2) these patterns can be efficiently and (ideally) automatically evaluated ( Bain, 2005 ; Ford, 2013 ).…”

Section: Introductionmentioning

confidence: 99%