Microscopic 3-Dimensional Reconstruction of Prostate Cancer Cell Network: An Innovative Approach To Perceive Tumor Invasion
AV Ugolkov, LJ Eisengart, Y Jiang, Y Peng, XJ Yang. Northwestern University, Chicago, IL; University of Chicago, Chicago, IL
Background: Conventional cancer research is based on microscopic observation of 2D (2-dimensional) section of tumor tissue. Matrigel in vitro experiments and 2D tumor sections give an impression that cancer cells can migrate withing normal tissue supporting epithelial-mesenchymal transition (EMT) theory. The aim of this study was to reconstruct microscopic 3D (3-dimensional) figure of prostate cancer cell network to address the question whether cancer cells can invade as migrating independent cells or small clumps of cells as seen on 2D tumor section.
Design: To facilitate a subsequent detection of cancer cells using computer image-analysis techniques, E-cadherin immunostaining was performed using 100 serial prostate cancer sections. We developed and used a software which allows to recognize malignant cells (brown) vs. stromal cells (blue). In order to expand conventional 100 serial 2D images into one 3D figure of prostate tumor, we used computer image-analysis techniques.
Results: We selected the area of tumor invasion front representing mostly prostate cancer cells surrounded by stromal cells. After scanning of 100 serial 2D tumor sections stained for E-cadherin and subsequent recognition of E-cadherin positive cancer cells by software, we used computer image-analysis techniques to delete benign epithelial and stromal cells from images and reconstruct prostate cancer cell network in 3D. We found that cancer cells are not separated (as seen on 2D section) but connected forming cancer cell network in 3D figure resembling "hair ball" where free of cancer cell space is filled with benign cells. Our results suggest that tumor invasion is driven by not migration but proliferation of cancer cells leading to elongation of tumor invasion roots and formation of new buds or branches from existing roots.
Conclusions: 3D histology is an innovative concept that challenges conventional concepts of cancer invasion based on analysis of 2D tumor sections. Our analysis of 3D configuration of prostate cancer cell network suggests proliferation of cancer cells leading to formation of tumor invasion roots as a critical determinant of microscopic tumor invasion. By careful reconstruction and investigation of 3D microscopic figure of tumor, we can achieve a better understanding of tumor invasion which could be a basis for the development of new approaches in cancer prevention and therapy.
Wednesday, March 24, 2010 9:30 AM
Poster Session V # 213, Wednesday Morning