Senescent tumor cells lead the collective invasion in thyroid cancer

Nat Commun. 2017 May 10:8:15208. doi: 10.1038/ncomms15208.

Abstract

Cellular senescence has been perceived as a barrier against carcinogenesis. However, the senescence-associated secretory phenotype (SASP) of senescent cells can promote tumorigenesis. Here, we show senescent tumour cells are frequently present in the front region of collective invasion of papillary thyroid carcinoma (PTC), as well as lymphatic channels and metastatic foci of lymph nodes. In in vitro invasion analysis, senescent tumour cells exhibit high invasion ability as compared with non-senescent tumour cells through SASP expression. Collective invasion in PTC is led by senescent tumour cells characterized by generation of a C-X-C-motif ligand (CXCL)12 chemokine gradient in the front region. Furthermore, senescent cells increase the survival of cancer cells via CXCL12/CXCR4 signalling. An orthotopic xenograft in vivo model also shows higher lymphatic vessels involvement in the group co-transplanted with senescent cells and cancer cells. These findings suggest that senescent cells are actively involved in the collective invasion and metastasis of PTC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Papillary / genetics
  • Carcinoma, Papillary / metabolism
  • Carcinoma, Papillary / pathology*
  • Cell Line, Tumor
  • Cell Movement*
  • Cells, Cultured
  • Cellular Senescence*
  • Chemokine CXCL12 / genetics
  • Chemokine CXCL12 / metabolism
  • Female
  • Gene Expression Profiling
  • Humans
  • Lymphatic Metastasis
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Invasiveness
  • Receptors, CXCR4 / genetics
  • Receptors, CXCR4 / metabolism
  • Thyroid Epithelial Cells / metabolism
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / metabolism
  • Thyroid Neoplasms / pathology*
  • Transplantation, Heterologous

Substances

  • CXCL12 protein, human
  • CXCR4 protein, human
  • Chemokine CXCL12
  • Receptors, CXCR4