What influences how a cancer cell behaves? Is it all inside the cell? Or does the cell respond to it’s environment? Nature or nurture? Many recent studies have found that tumor cell behavior (including response to therapy!) is very much nurture or environment dependent. These findings have led us to ask: (1) what is the environment of a tumor like and (2) how does this environment change how cancer cells behave?

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 quantitative mass spec metabolomics methods 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.

Upper Method that is used to generate stable isotope labeled internal standards that allows for quantitative metabolomics of IF. Lower Absolute concentration of many nutrients in the IF or environment of pancreatic tumors.

Determining how the environment influences cell behavior

With this insight into the environment of tumors, 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 nutrient composition of IF, and we can grow cancer cells in this fluid. We are performing a number of analysis on IF-exposed cells to determine how cancer cells behave in IF-like conditions, including genetic screens to identify genes that cancer cells require to survive IF conditions, possibly identifying new drug targets.

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. We are determining if the IF environment of tumors alters immune cell behavior and prevents the immune cells from combating tumors.