205P - Visualizing ZO-1-mediated coupled migration between cancer and stromal cells in lung cancer metastasis via a 5-dimensional cell imaging system

Date 15 April 2016
Event European Lung Cancer Conference 2016 (ELCC) 2016
Session Poster lunch
Topics Staging procedures (clinical staging)
Thoracic malignancies
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Imaging
Presenter Hsuan-Hsuan Lu
Citation Journal of Thoracic Oncology (2016) 11 (supplement 4): S57-S166. S1556-0864(16)X0004-4
Authors H. Lu1, B. Chen2, H. Chen3, C. Ho1, C. Yu1
  • 1Department Of Internal Medicine, National Taiwan University Hospital, 100 - Taipei/TW
  • 2Research Center For Applied Science, Academia Sinica, 11529 - Taipei/TW
  • 3Graduate Institute Of Toxicology, National Taiwan University NTU, College of Medicine, Taipei/TW

Abstract

Background

A long-standing question concerns how cancer cells efficiently travel from primary tumor to distant metastases. The unique roles of microenvironment are also been studied, including cancer associated fibroblasts (CAFs), tumor associated macrophages, and endothelial cells. However, the initiation stage of metastasis is still unknown. In this study, we present the crucial role of ZO-1 in coupled migration regulated by CAFs in lung cancer metastasis.

Methods

CD90+ CAFs were isolated from tumor tissue of lung cancer patients. A matrigel-based 3-Dimensional (3-D) co-culture system was established to study the interaction between cancer and CAFs in vitro. To further investigate the interaction between cancer cells and CAFs, we used lattice light-sheet microscopy system to perform a rapid time-lapse imaging system, including three spatial-temporal model, and the excitation and imaging of several spectrally separated fluorophore labels i.e. 5D to observe the real-time motion and cell-cell coordinated migration.

Results

Lung cancer cell lines and CAFs were co-cultured in the 3-D system. Cancer cells and CAFs could form a systemic structure in a very short time point (∼4 h) through the direct contact interaction. Via confocal microscopy and lattice light-sheet microscopy, we found there were bridge-like structures formed by CAFs, and CAFs would carry cancer cells to move together as the coupled migration. Furthermore, CAFs not only significantly promoted invasion ability of cancer cells in in vitro assay (>4 folds), but also enhanced cancer metastasis in orthotropic injection model (>3 folds). ZO-1 in CAFs seems play a pivotal role in the coupled migration of metastasis processes. Knockdown of ZO-1 in CAFs resulted in dramatically cutback the interaction between cancer cells and CAFs.

Conclusions

These results propose that CAFs play imperative roles in the initiation stage of cancer metastasis via coupled migration and the direction of movement. It also implies that the interaction between cancer cells and CAFs might be a novel treatment strategy in cancer metastasis by targeting the direct contact components between cancer cells and CAFs.

Legal entity responsible for the study

National Taiwan University College of Medicine

Funding

Ministry of Science and Technology (TAIWAN) MOST 104-2314-B-002-173-MY3

Disclosure

All authors have declared no conflicts of interest.