“When a plant goes to seed, its seeds are carried in all directions; but they can only live and grow if they fall on congenial soil. While many researchers have been studying ‘the seeds’, the properties of ‘the soils’ may reveal valuable insights into the peculiarities of cancer cases.” -Stephen Paget, 1889
What influences how a cancer behaves? Is it all programmed in the cancer itself, ‘the seed’? Or does is the cancer influenced by to it’s environment, ‘the soil’? Nature or nurture? Decades of research have affirmed Paget’s hypothesis that understanding both the seed and the soil are both equally critical for understanding the properties of tumors. Given how critical understanding the environment of tumors is to understanding how cancers work, our group develops technologies to uncover: (1) what the environment of tumors are like and (2) how these environmental conditions interaction with cancer cells to change their properties and behavior.
Characterizing the tumor environment
Cancer cells are bathed in a fluid called, interstitial fluid (IF). IF provides nutrients, and delivers messages in the form of signaling factors to cancer cells in the tumor. Thus, IF is a critical component of the environment of a tumor. We have recently developed methods to isolate IF from tumors, and combined this with new analytical technologies to analyze what nutrients and signaling factors are present in the tumor environment. We are currently using these techniques to determine if every type of tumor has the same environment, or if each is different. We are also learning if primary tumors have the same environment as distant metastases that come from the primary tumor. Lastly, we are asking how the tumor environment changes as tumors progress and grow, or regress during treatment. These experiments will give us new insight into the environment of tumors, and what determines what the environment of a tumor is like.
Determining how the environment influences cell behavior
Now that we know what is in the tumor environment, we are now asking how cancer cell behavior is influenced by the tumor environment. To do this, we have made a fluid that approximates the composition of IF, and we can grow cancer cells in this fluid. This let’s us study not just ‘the seeds’ in isolation, but as ‘the seeds’ interact with their native ‘soil’. We are performing a number of analyses on IF-exposed cells to determine how cancer cells behave in IF-like conditions, including genetic and drug screens to identify new ways to target tumors. Our long term vision is to learn how to treat cancers by not just targeting the the cancer cells themselves, but how the cancer cells interact with their environment.
Beyond the cancer cells themselves, we are also interested in how IF influences the behavior of other cells in the tumor, especially immune cells. Immune cells can often control tumors by killing cancer cells, but in some tumors immune cells lose this ability. With collaborators at the University of Pittsburgh, we are determining how the IF environment of tumors alters immune cell behavior and prevents the immune cells from combating tumors.