Nab-paclitaxel interrupts cancer-stromal interaction through C-X-C motif chemokine 10-mediated interleukin-6 downregulation in vitro

Cancer Sci. 2018 Aug;109(8):2509-2519. doi: 10.1111/cas.13694. Epub 2018 Jul 9.

Abstract

Cancer-associated fibroblasts (CAF), derived from stroma of cancer tissues, interact with cancer cells and play an important role in cancer initiation, growth, and metastasis. Nab-paclitaxel (nab-PTX) is a 130 nm albumin-binding paclitaxel and recommended for many types of cancer chemotherapy. The nab-PTX stromal-disrupting effect during pancreatic cancer treatment has been reported. The aim of the present study was to determine the role of nab-PTX in cancer cells and CAF interaction. Cancer cells (MIA PaCa-2 and Panc-1) were cocultured with CAF or treated with CAF conditioned medium, after which their migration and invasion ability, epithelial-mesenchymal transition (EMT)-related marker expression and C-X-C motif chemokine 10 (CXCL10) expression and secretion were detected. Nab-PTX treatment was carried out during the coculture system or during preparation of CAF conditioned medium. Then cancer cell migration and invasion ability, EMT-related marker expression, CXCL10 expression and secretion, and interleukin-6 (IL-6) expression and secretion by CAF were checked After coculture with CAF, migration and invasion ability of cancer cells increased. CAF also downregulated E-cadherin and upregulated N-cadherin and vimentin expression in cancer cells. During coculture or stimulation with cancer cell-cultured medium, CAF significantly increased IL-6 expression and secretion. However, nab-PTX in the coculture system canceled CAF-induced migration and invasion promotion and EMT-related gene changes. Moreover, nab-PTX increased CXCL10 expression of cancer cells which blocked CAF IL-6 expression and secretion. Nab-PTX treatment could increase CXCL10 expression of cancer cells which blocks CAF cancer cell migration and invasion-promoting effect by inhibiting IL-6 expression.

Keywords: 130 nm albumin-bound paclitaxel; cancer-associated fibroblast; chemokine CXCL10; epithelial-mesenchymal transition; pancreatic neoplasms.

MeSH terms

  • Albumins / pharmacology*
  • Biomarkers, Tumor / metabolism
  • Cadherins / metabolism
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Chemokine CXCL10 / metabolism*
  • Coculture Techniques
  • Down-Regulation / drug effects*
  • Epithelial-Mesenchymal Transition / drug effects
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Humans
  • Interleukin-10 / metabolism
  • Interleukin-6 / metabolism*
  • Neoplasm Invasiveness / pathology
  • Paclitaxel / pharmacology*
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / metabolism
  • Up-Regulation / drug effects
  • Vimentin / metabolism

Substances

  • 130-nm albumin-bound paclitaxel
  • Albumins
  • Biomarkers, Tumor
  • CXCL10 protein, human
  • Cadherins
  • Chemokine CXCL10
  • Interleukin-6
  • Vimentin
  • Interleukin-10
  • Paclitaxel