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Related Concept Videos

Somatic to iPS Cell Reprogramming01:29

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Distinct Chemical Cues Reprogram Cellular and Multicellular Phenotypes in Ovarian Cancer Spheroids.

M Sreepadmanabh1, Meenakshi Ganesh1, Jimpi Langthasa2,3

  • 1National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, 560065, India.

Small (Weinheim an Der Bergstrasse, Germany)
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Cancer cell aggregates can reorganize and recover from damage. Calcium and pH levels control cell states and structural dynamics, offering insights into cancer metastasis and resilience.

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biochemical regulationcancer spheroidschemical reprogrammingmulticellular collectivesovarian cancer

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Area of Science:

  • Cellular biology
  • Developmental biology
  • Cancer research

Background:

  • Cellular collective self-organization is vital for development and cancer progression.
  • Multicellular cancer aggregates exhibit increased metastatic potential, but the underlying mechanisms are unclear.
  • Mechanochemical cues influencing the organization and stability of cellular ensembles require further investigation.

Purpose of the Study:

  • To investigate the role of mechanochemical microenvironmental cues in regulating the self-organization and stability of ovarian cancer spheroids.
  • To identify specific cues that govern the transition between different structural states in cellular collectives.
  • To understand the mechanisms behind the structural resilience and plasticity of cancer cell assemblies.

Main Methods:

  • Utilized a model system of ovarian cancer spheroids exhibiting transitions from moruloids to blastuloids.
  • Analyzed periodic volume fluctuations in blastuloids, linking them to lumenal fluid influx and cell-cell junctional states.
  • Employed targeted chemical perturbations to identify regulatory cues for transition traits.

Main Results:

  • Demonstrated that periodic volume fluctuations in blastuloids are driven by lumenal fluid influx and cell-cell junctional states.
  • Showed that blastuloid cells can reprogram their states, enabling rapid recovery from structural disintegration and self-organization into lumenized ensembles.
  • Identified calcium levels as regulators of cell states and pH as a regulator of blastuloid phenotype fluctuation dynamics.

Conclusions:

  • Ovarian cancer spheroid structural plasticity and resilience are regulated by specific mechanochemical cues.
  • Calcium and pH play distinct roles in controlling cell state reprogramming and dynamic phenotypic fluctuations, respectively.
  • Findings provide critical insights into the mechanisms governing structural resilience in complex cellular assemblies, with implications for cancer metastasis.