Extracellular matrix invasion in metastases and angiogenesis: Commentary on the Matrigel "chemoinvasion assay"

Invasive and metastatic cells must cross the basement membrane's extracellular matrix to disseminate to distant sites. Although in the eighties the concept was well established, no easy in vitro functional assay was available. Working in Hynda Kleinman's and George Martin's laboratory at NIH (Bethesda, MD), where the reconstituted basement membrane Matrigel was discovered, I had the intuition that Matrigel coating of migration filters could represent a valid tool to mimic in vitro biological matrix barriers. The "chemoinvasion assay" using Matrigel in Boyden blind-well chambers was developed in 1985-1986 and published in Cancer Research in 1987. It was a rapid and easy tool for studying invasion, a crucial step in cancer metastasis. Since its conception, the assay has been employed for studies on the metastatic process, angiogenesis, and for the screening of drugs that are potentially able to decrease cell invasion. It was adapted to be easily employed as a routine assay and commercialized. In that historical article, we also described the use of thick layers of Matrigel for the study of morphogenesis of invasive cells, a simple and visual assay, adaptable to reproduce collective cell migration in vitro. To date, in its diverse optimized variants, the chemoinvasion assay is still widely used, contributing to novel data production. In the era of precision medicine and next-generation sequencing, the cheap, fast, and reproducible chemoinvasion assay may have further developments, including possible applications in the investigations on cancer stem cells, immunity and immune modulators, applications with siRNA silencing, selection of aggressive cell populations, and phenotypes and genetic evaluations. Cancer Res; 76(16); 4595-7.