Environmental Factor, October 2005, National Institute of Environmental Health Sciences
Hendrix Delivers Season's First Distinguished Lecture
By Blondell Peterson
Mary J. C. Hendrix, professor of pediatrics at Northwestern University's Feinberg School of Medicine and President and Scientific Director of the Children's Memorial Research Center at Northwestern University, lectured on "The Epigenetic Influence of the Microenvironment on Cell Plasticity" on September 14 at the Rodbell Conference Center. The lecture was the first of this academic season's Distinguished Lecture Series.
"Mary is one of the pioneers of developing techniques to understand molecular mechanisms of metastasis," said Deputy Scientific Director Steven Akiyama and host for the lecture. "She developed some of the earliest in vitro invasion assays that are still in use today to try to understand the fundamental steps in this very complex process."
Although they didn't realize there was a common thread at the time, Hendrix said scientists in her lab looked at properties that tumors and embryos share in common. It turns out they share many common properties, for example both tumors and embryos require a blood supply for growth.
"What's interesting to note is that the very first type of blood supply in an embryo is formed through a process known as vasculogenesis," she said. While she showed an artists rendition in a slide of how stem cells begin to coalesce during vasculogenesis, she went on to say that they differentiate into endothelial cells. These endothelial cells will form these primitive vasculogenic networks.
Other properties that embryos and tumors share in common that are becoming much more apparent with microarray analysis, according to Hendrix, are that they share common stem cell markers.
She said a question that has been a little puzzling for some scientists is, "Why do tumor cells that are highly aggressive look very much like embryonic stem cells?"
Hendrix also talked about the role of microenvironment in shaping and affecting tumor cell plasticity. In particular, she discussed one of the examples of tumor cell plasticity that researchers found in her lab and reported on in 1999, called vasculogenic mimicry.
They made the discovery by placing metastatic human melanoma cells in a three dimensional type 1 collagen matrix. The first observation of the culture occurred three days later when a researcher noticed these metastatic melanoma cells formed extracellular matrix rich networks. These network structures look very similar and mimicked these primitive vasculogenic type networks.
"Our lab has been trying to understand what the molecular and cellular determinants are underlying vasculogenic mimicry in really looking at this as just an example of tumor cell plasticity," she said. "More recently we've been looking at the role of the tumor microenvironment in contributing to this particular phenotype."
Hendrix said scientists in her lab have looked at close to 30 human melanoma cell lines divided into poorly aggressive versus highly aggressive cells. While she showed pictures of the cells on tissue culture plastic, Hendrix said it's always important to look at cells in many different environments. Her lab would never have made the observation of vasculogenic mimicry if they had not taken cultures from tissue culture plastic and placed them in a three dimensional matrix.