Vanderbilt-Ingram Receives Grant to Study Tumor Environment
By Heather Newman
Like a seed needs soil to grow and flourish, a tumor relies on its environment to grow and spread in the body, something the Vanderbilt-Ingram Cancer Center will be exploring more closely with the help of a grant from the National Cancer Institute (NCI) for $1.3 million a year for the next five years.
It’s a new type of grant from the NCI, sparked in part by a new wave of interest and attention to the microenvironment of a tumor, making it the latest hot-button word in cancer research. “We have been looking specifically at what was inside the cancer cell. We were really focused on the seed and we forgot about the soil,” said Lynn Matrisian, Ph.D., Chair of Cancer Biology at Vanderbilt-Ingram.
But Matrisian said the tide has turned and experts are focusing attention on the soil or tumor environment, something that could alter cancer outcomes if the soil is tended well. “The microenvironment can tell the cancer cells to behave normally. We think there’s incredible opportunity for targeting the microenvironment and potentially finding new treatment options.”
Matrisian said some drugs on the market already focus on the tumor environment. “The angiogenesis drugs target the microenvironment and the body’s response to the tumor and don’t target the tumor itself,” explained Matrisian. Avastin, recently approved by the Food and Drug Administration to treat advanced, non-squamous, non-small cell lung cancer, and studied here at Vanderbilt-Ingram, is one of those drugs.
The NCI grant will allow Vanderbilt-Ingram to become a key player in a new network of investigators looking at the microenvironment and researching different areas related to the soil where the tumor sets up camp. Members of the network will meet twice a year to share discoveries.
Other groups in the network include Harvard-MIT, Memorial Sloan Kettering Cancer Center, Baylor College of Medicine, Columbia University, Lawrence Berkeley National Laboratories, the Albert Einstein Cancer Center, and the Fred Hutchinson Cancer Research Center. Vanderbilt-Ingram will also work closely with a group from Dana Farber as part of the project.
Vanderbilt’s participation will involve three research projects zeroing in on a molecule called TGF-_ that Matrisian said could prove to be the key to host-tumor interactions. “We went with a molecular focus because we think this molecule is really important. If we can find out how the microenvironment reacts to TGF-_ in these three settings, it could apply to many cancers.”
The first project, led by Harold L. Moses, M.D., Director Emeritus of Vanderbilt-Ingram and the Hortense B. Ingram Professor of Molecular Oncology, is a breast cancer study aimed at uncovering the TGF-_ response to the environment. “Manipulating the TGF-_ response in the normal cells makes the tumor much worse than manipulating this molecule in the tumor cells itself,” said Matrisian, again adding to the theory behind the importance of the environment hosting the tumor.
The second project under the grant will be led by Simon Hayward, Ph.D. and Neil Bhowmick, Ph.D. in the Departments of Urologic Surgery and Cancer Biology, and will focus on prostate cancer. The study will involve taking prostate cancer cells and normal cells and putting them together to manipulate and influence the genes in the tumor.
The third project, led by Gregory Mundy, M.D., John A. Oates Chair in Translational Medicine and Director of the Vanderbilt Center for Bone Biology, will spotlight bone metastasis. “Breast and prostate cancer both go to the bone,” said Matrisian. “Tumor cells tell the bone cells to degrade the bone. TGF-_ in the bone gets released and makes the tumor cells grow and be worse,” she said. “We want to know why this is happening, how TGF-_ is doing this and what is downstream from the effect.”
Matrisian said she believes Vanderbilt-Ingram’s proposal and all three projects were funded, in part, because of the supporting technology available here. The proteomics involved in the studies will benefit from the mass spectrometry experts on campus. “A lot of people are looking at genes or genomics. We’re looking at proteins or proteomics.” Matrisian said the researchers will work closely with John Gore, Ph.D., Professor and Director of the Vanderbilt University Institute of Imaging Science, to merge proteomics, oxygen, and blood flow images into one picture of the tumor and its environment.
In addition, the math model developed in collaboration with Vanderbilt-Ingram’s Integrative Cancer Biology Center, led by Vito Quaranta, M.D., Professor of Cancer Biology, will help researchers approach the tumor-host environment from a systems biology approach. “I don’t think anyone else proposed that,” said Matrisian.
However, Matrisian said this is discovery research, not translational. Meaning, don’t expect to see the findings in these projects applied to treatments and patients next month. “We can make this translational before too long. The real challenge is to sort through all that information first to know which way to go.”
