| Abstract: |
| A major reason for cancer treatment failure and disease progression is a
heterogeneous composition of tumor cells at the genetic, epigenetic, and
phenotypic levels. While tremendous efforts have tried to characterize the
makeups of single cells, much less is known about interactions between
heterogeneous cancer cells and between cancer cells and the
microenvironment in the context of cancer invasion. Clinical studies show
that invasion predominantly occurs via collective invasion packs, which
invade more aggressively and result in worse outcomes. Using non-small
cell lung cancer spheroids in collagen, we show that the invasion packs
consist of leaders and followers. In vitro and in silico experiments show
that leaders and followers engage in mutualistic social interactions
during collective invasion. Many fundamental questions remain: What is the
division of labor within the heterogeneous invasion pack? How does the
leaders emerge? How do the invasion packs interact with the stroma? Can
the social interaction network be exploited to devise novel treatment
strategies? I will present the recent experimental and modeling efforts
that address these questions. Analyzing this social interaction network
can potentially reveal the `weak-links`, which when perturbed can disrupt
collective invasion. |
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