header logo image header logo text
Downloads Login
Research
General Information
ZIRC
ZFIN ID: ZDB-PUB-170420-13
A zebrafish model discovers a novel mechanism of stromal fibroblast-mediated cancer metastasis
Liu, C.F., Zhang, Y., Lim, S., Hosaka, K., Yang, Y., Pavlova, T., Alkasalias, T., Hartman, J., Jensen, L., Xing, X.M., Wang, X., Lu, Y.T., Nie, G.H., Cao, Y.
Date: 2017
Source: Clinical cancer research : an official journal of the American Association for Cancer Research   23(16): 4769-4779 (Journal)
Registered Authors:
Keywords: none
MeSH Terms:
  • A549 Cells
  • Animals
  • Animals, Genetically Modified
  • Cancer-Associated Fibroblasts/metabolism
  • Cancer-Associated Fibroblasts/pathology*
  • Cancer-Associated Fibroblasts/transplantation
  • Cell Line, Tumor
  • Cell Movement/genetics
  • Embryo, Nonmammalian/embryology
  • Embryo, Nonmammalian/metabolism
  • Embryo, Nonmammalian/pathology*
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasms/genetics
  • Neoplasms/metabolism
  • Neoplasms/pathology*
  • Transplantation, Heterologous
  • Zebrafish/embryology*
  • Zebrafish/genetics
PubMed: 28420724 Full text @ Clin. Cancer Res.
FIGURES
ABSTRACT
Purpose: Cancer metastasis can occur at the early stage of tumor development when a primary tumor is at the microscopic size. In particular, the interaction of malignant cells with other cell types including cancer-associated fibroblasts (CAF) in promoting metastasis at the early stage of tumor development remains largely unknown. Here, we investigated the role of CAFs in facilitating the initial events of cancer metastasis when primary tumors were at microscopic sizes.Experimental Design: Multicolor-coded cancer cells and CAFs were coimplanted into the transparent zebrafish body and metastasis at a single-cell level was monitored in living animals. Healthy fibroblasts, tumor factor-educated fibroblasts, and CAFs isolated from various tumors were tested for their ability to facilitate metastasis.Results: We showed that CAFs promoted cancer cell metastasis at the very early stage during primary tumor development. When a primary tumor was at the microscopic size consisting of a few hundred cells, CAFs were able to hijack cancer cells for dissemination from the primary site. Surprisingly, a majority of metastatic cancer cells remained in tight association with CAFs in the circulation. Furthermore, stimulation of non-metastasis-promoting normal fibroblasts with TGF-B, FGF-2, HGF, and PDGF-BB led to acquisition of their metastatic capacity.Conclusions: Cancer metastasis occurs at the very early stage of tumor formation consisting of only a few hundred cells. CAFs are the key cellular determinant for metastasis. Our findings provide novel mechanistic insights on CAFs in promoting cancer metastasis and targeting CAFs for cancer therapy should be aimed at the early stage during cancer development. Clin Cancer Res; 23(16); 4769-79. ©2017 AACR.
ADDITIONAL INFORMATION