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Dimensional Priming Reprograms Adipose-Derived Stromal Cells to Promote Pancreatic Cancer Progression.

Bo Han1,2, Zhi Yang1, Shuqing Zhao1

  • 1Departments of Surgery, University of Southern California, Los Angeles, CA 90033, USA.

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Summary

Dimensional priming of adipose-derived stromal cells (ADSCs) significantly alters their behavior, with 3D cultures promoting pancreatic ductal adenocarcinoma (PDAC) growth and invasion, unlike 2D cultures which suppress it. This highlights mechanical cues as key regulators in the PDAC tumor microenvironment.

Keywords:
3D culture systemsPDACadipose-derived stromal cellsdimensional primingmatrix mechanicsstromal plasticity

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Area of Science:

  • Cancer Biology
  • Biomaterials Science
  • Immunology

Background:

  • The tumor microenvironment (TME) is crucial in pancreatic ductal adenocarcinoma (PDAC) progression.
  • Mechanical cues influencing stromal cell behavior in the TME are not well understood.

Purpose of the Study:

  • To investigate how dimensional priming of adipose-derived stromal cells (ADSCs) affects their immunomodulatory functions.
  • To determine the impact of dimensional priming on PDAC growth.

Main Methods:

  • ADSCs were cultured in 2D and 3D conditions.
  • In vitro co-culture with PDAC organoids and in vivo xenograft models were used.
  • Stromal phenotype, cytokine secretion, tumor growth, invasion, and immune cell infiltration were assessed.

Main Results:

  • 3D-primed ADSCs adopted a CAF-like phenotype with reduced CAV-1, promoting PDAC migration and growth via soluble factors (IL-6, TNF-α).
  • 2D-primed ADSCs suppressed PDAC growth and invasion in vitro and in vivo, maintaining tumor boundaries.
  • 3D-primed ADSCs led to larger tumors with aggressive invasion, while 2D-primed ADSCs suppressed growth and macrophage infiltration was highest in 2D-primed tumors.

Conclusions:

  • Dimensional priming fundamentally reprograms ADSC phenotype and stromal-immune interactions.
  • This reprogramming generates a tumor-permissive state that accelerates PDAC progression.
  • Mechanical cues are critical regulators of stromal plasticity within the PDAC microenvironment.