Molecular Understanding of Vasculogenic Mimicry in SCLC

Co-targeting neuroendocrine (NE) and non-NE cells may help reduce small cell lung cancer (SCLC) progression, according to recent study findings, and thus improve patient outcomes.

Researchers in the United States and United Kingdom, led by Sarah M. Pearsall, a doctoral student, analyzed perfusion within vasculogenic mimicry (VM) vessels and their association with NE and non-NE phenotypes in circulating tumor cell-derived explant (CDX) models, genetically engineered mouse models (GEMMs), and 20 patient biopsies positive for SCLC. They used multiplex immunohistochemistry to do so.

The study results showed VM vessels in 23 of 25 CDX models, two GEMMS, and 20 biopsies. “Perfused VM vessels support tumor growth, and only NOTCH-active non-NE cells are VM-competent in vivo and ex vivo, expressing pseudohypoxia, blood vessel development, and extracellular matrix organization signatures,” the authors wrote.

Furthermore, on Matrigel, VM-primed non-NE cells remodel extracellular matrix into hollow tubules in an integrin β1-dependent process. “This study strongly recommends that therapeutic strategies should broaden beyond targeting NE biology and co-target VM-competent non-NE cells,” the authors wrote.

The findings are a step forward in understanding the molecular events that enable VM, according to the authors.