Signs of aggression
In the rogue's gallery of metastatic cells, some are more aggressive — more footloose, intrusive, and ultimately more treacherous — than others. Dana-Farber's Penelope Miron, PhD, and Maren Chan, MD, are seeking the genetic underpinnings of this variability.
Preventing metastasis - or halting it, slowing it, or somehow rendering it less harmful - is especially important because 90 percent of cancer deaths result from metastatic tumors.
Their particular quarry is ductal carcinoma in situ (DCIS), a form of cancer normally confined to the milk ducts of the breast, but which sometimes gains the ability to spread to nearby tissue. Almost always curable if caught early, the disease is diagnosed in nearly 45,000 American women each year.
By transplanting DCIS tissue into five successive groups of laboratory animals, Miron and Chan caused the cancer to morph into more and more aggressive forms. They collected tumor samples from each group and, using "gene chip" technology, studied the patterns of gene expression. "Genetic changes offer a window into how cells become more invasive," Miron says. Our hope is to uncover the key players involved in this process."
She and Chan have scanned the gene activity of only a handful of tumor samples so far, but already there is a surprise. Though some genes, as expected, seem to alter their activity levels as tumors grow more aggressive, the differences in gene signature between first- and fifth-generation transplanted cells were less striking than those between the individual families, or "lines," of tumor cells.
"It may turn out that once the basic signatures of the tumors were set, they didn't change that much with each successive transplantation," Miron observes. It's also possible that the analyzed samples came from less-invasive portions of the tumors. In any event, it's too early to draw conclusions; the majority of tissue samples have yet to be studied, and Miron expects that continued analysis will locate markers for tumors' aggressiveness.
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