Fibroblasts generate topographical cues that steer cancer cell migration

Sci Adv. 2023 Aug 18;9(33):eade2120. doi: 10.1126/sciadv.ade2120. Epub 2023 Aug 16.

Abstract

Fibroblasts play a fundamental role in tumor development. Among other functions, they regulate cancer cells' migration through rearranging the extracellular matrix, secreting soluble factors, and establishing direct physical contacts with cancer cells. Here, we report that migrating fibroblasts deposit on the substrate a network of tubular structures that serves as a guidance cue for cancer cell migration. Such membranous tubular network, hereafter called tracks, is stably anchored to the substrate in a β5-integrin-dependent manner. We found that cancer cells specifically adhere to tracks by using clathrin-coated structures that pinch and engulf tracks. Tracks thus represent a spatial memory of fibroblast migration paths that is read and erased by cancer cells directionally migrating along them. We propose that fibroblast tracks represent a topography-based intercellular communication system capable of steering cancer cell migration.

MeSH terms

  • Cell Movement / physiology
  • Cues*
  • Extracellular Matrix
  • Fibroblasts / physiology
  • Humans
  • Neoplasms*