HMGB1-containing nucleosome mediates chemotherapy-induced metastasis of human lung cancer

Biochem Biophys Res Commun. 2018 Jun 7;500(3):758-764. doi: 10.1016/j.bbrc.2018.04.150. Epub 2018 Apr 24.

Abstract

While chemotherapy is an important and widely used therapeutic for cancer, it may facilitate cancer metastasis. Herein, we report that human lung cancer cells exert higher invasion and metastasis after chemotherapy. In a human lung cancer xenograft model, chemotherapy promotes the cancer invasion and metastasis in HMGB1-dependent manner. Further studies identify HMGB1-containing nucleosome from chemotherapy-induced apoptotic cancer cells as an effective factor. Such nucleosome functions through TLR4 and TLR9 to drive cancer invasion and metastasis. In lung cancer patients, circulating HMGB1-containing nucleosome is higher in those under chemotherapy, predicting poorly cancer cell differentiation state, enhanced cancer invasion and advanced TNM stages. These findings provide a novel mechanism by which the tumor metastasis is propagated in lung cancer patients, especially in those under chemotherapy, and a clue for developing therapeutic strategies against chemotherapy-induced metastasis.

Keywords: Chemotherapy; HMGB1; Lung cancer; Nucleosome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Disease Progression
  • HMGB1 Protein / metabolism*
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology*
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Nucleosomes / metabolism*
  • Toll-Like Receptors / metabolism

Substances

  • HMGB1 Protein
  • Nucleosomes
  • Toll-Like Receptors