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A 3D Spheroid Model as a More Physiological System for Cancer-Associated Fibroblasts Differentiation and Invasion In Vitro Studies

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Circulating tumor cells from 4D model have less integrin beta 4 expression.

Dhruva K Mishra¹, Kenneth L Scott², Joanna M Wardwell-Ozgo²

¹Department of Surgery, Houston Methodist Research Institute, Houston, Texas.

The Journal of Surgical Research

|September 20, 2014

Summary

This summary is machine-generated.

A novel four-dimensional (4D) lung cancer model successfully isolates circulating tumor cells (CTCs). These 4D-derived CTCs exhibit distinct properties, including reduced adhesion and slower growth, crucial for metastasis.

Keywords:

4D model Circulating tumor cells Ex vivo Lung cancer

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Micromanipulation of Circulating Tumor Cells for Downstream Molecular Analysis and Metastatic Potential Assessment

Micromanipulation of Circulating Tumor Cells for Downstream Molecular Analysis and Metastatic Potential Assessment

Published on: May 14, 2019

Area of Science:

Oncology
Cell Biology
Biotechnology

Background:

Limited in vitro/ex vivo models for isolating circulating tumor cells (CTCs).
Development of a novel four-dimensional (4D) lung cancer model for CTC isolation.
Hypothesis that 4D-derived CTCs possess different properties than traditional 2D cultured cells.

Purpose of the Study:

To characterize circulating tumor cells (CTCs) isolated using a 4D lung cancer model.
To compare the properties of CTCs derived from the 4D model with parental 2D cells.
To investigate the role of cell adhesion molecules, specifically Integrin beta 4 (ITGB4), in CTC behavior.

Main Methods:

Generated CTCs from A549, H1299, 393P, and 344SQ cell lines using the 4D lung model.
Performed in vitro functional characterization of CTCs.
Compared gene expression of cell adhesion molecules between 4D-derived CTCs and 2D cells.
Investigated ITGB4 function through stable transfection in A549 and H1299 cells.

Main Results:

All tested cell lines produced CTCs using the 4D model.
CTCs from the 4D model showed significantly reduced adherence and slower growth rates compared to 2D cells (P < 0.01).
Most cell adhesion molecules were downregulated in CTCs (P < 0.05), with ITGB4 being significantly underexpressed across all cell lines.
Modulation of ITGB4 resulted in differential functional changes in 2D cells.

Conclusions:

CTCs derived from the 4D lung model exhibit distinct transcriptional, translational, and in vitro characteristics compared to 2D cultured cells.
The 4D-derived CTCs possess properties associated with metastatic potential.
The 4D model provides a valuable tool for studying CTCs and their role in cancer metastasis.