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Efficient extravasation of tumor-repopulating cells depends on cell deformability

Junjian Chen1, Wenwen Zhou1, Qiong Jia1

  • 1Laboratory for Cellular Biomechanics and Regenerative Medicine, Department of Biomedical Engineering, School of Life Sciences, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China.

Scientific Reports
|January 21, 2016
PubMed

Insights

Tumor cell deformability, influenced by Sox2 and Cdc42, is key for cancer metastasis. This study shows more deformable tumor-repopulating cells (TRCs) efficiently form micrometastases in zebrafish embryos.

Area of Science:

  • Oncology
  • Developmental Biology
  • Cell Biology

Background:

  • Cancer metastasis remains a major challenge, with few cells initiating secondary tumors.
  • Tumor-repopulating cells (TRCs) are a highly tumorigenic subpopulation identified in 3D cultures.
  • Understanding the mechanisms of metastasis initiation is crucial for developing effective therapies.

Purpose of the Study:

  • To investigate the role of tumor cell properties in metastasis using a zebrafish embryo model.
  • To determine the factors influencing the metastatic efficiency of TRCs compared to control cells.
  • To elucidate the molecular mechanisms underlying TRC extravasation and colonization.

Main Methods:

  • Injection of mouse melanoma TRCs and control cells into zebrafish embryos (Tg (fli1:EGFP or kdrl:mCherry)).
  • 3D confocal microscopy to visualize TRC behavior at secondary sites.
  • Gene silencing (Sox2) and manipulation of cell signaling molecules (Cdc42) to assess their impact on metastasis.
  • In vitro transmigration assays to evaluate cell deformability.

Main Results:

  • TRCs exhibited significantly higher efficiency in survival, growth, micrometastasis, and metastatic colonization in zebrafish embryos compared to control cells.
  • TRC metastasis was dependent on Sox2; silencing Sox2 inhibited metastasis.
  • High-resolution imaging revealed more efficient extravasation and micrometastasis formation by TRCs.
  • TRC deformability, linked to low Cdc42 and high Sox2, was critical for efficient in vivo extravasation and in vitro transmigration.

Conclusions:

  • Tumor cell deformability is a critical determinant of extravasation dynamics and metastatic potential.
  • Sox2 plays a crucial role in promoting TRC metastasis, potentially by regulating cell deformability.
  • Targeting cell deformability could offer novel strategies to inhibit cancer metastasis.

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