Fox Chase Cancer Center Study: Pancreatic And Kidney Cancers Contain Noncancerous Niches That May Be Manipulated To Hinder Tumor Growth
PHILADELPHIA (January 31, 2017) – A team of researchers at Fox Chase Cancer Center has found that stroma – a tumor-associated niche containing noncancerous cells and extracellular proteins – carries a cellular signature indicating whether it is likely to promote or restrict the tumor’s growth. Further, stroma components that encourage tumor growth may be engineered to work against the tumor. Edna Cukierman, PhD, associate professor of cancer biology at Fox Chase, led a team that included pathologists, surgeons, statisticians, basic biologists, and computer scientists to produce the study, which appears in the journal eLife.
“Previous studies have shown that noncancerous components of pancreatic tumors can provide a niche in which cancer cells thrive, or one that is hostile to the tumor,” Cukierman said. “We found characteristics of the stroma that predicted each of these clinical outcomes.”
Using patients’ cells to engineer a system that mimics stroma, Cukierman and her team uncovered a series of biomarkers that included levels and localization of the active form of a cellular receptor known as alpha-5-beta-1 integrin. The researchers examined these markers in hundreds of pancreatic tumors from patients treated at Fox Chase, using a new software and microscopy technique that allowed them to distinguish biomarker levels in cancer and stromal cells. They observed that the stromal biomarkers indicating a tumor-impeding environment were evident in patients that presented with longer recurrence-free survival than patients in which the tissue samples lacked these traits.
Results also suggested that stromal cells affected by pancreatic or renal cancers have the ability to produce a niche associated with shorter overall survival. Importantly, the team uncovered means to alter cells and their extracellular niches to switch tumor-promoting stroma into tumor-impeding stroma.
“More study is ongoing, but our work suggests the possibility of developing therapies that could modify tumor-promoting stroma to hinder a tumor’s growth,” Cukierman said.
The Chinese Society of Clinical Oncology honored Cukierman for this study with its Distinguished Achievement Award in Cancer Research and Clinical Management with a Focus on Pancreas.
“Previous studies have shown that noncancerous components of pancreatic tumors can provide a niche in which cancer cells thrive, or one that is hostile to the tumor,” Cukierman said. “We found characteristics of the stroma that predicted each of these clinical outcomes.”
Using patients’ cells to engineer a system that mimics stroma, Cukierman and her team uncovered a series of biomarkers that included levels and localization of the active form of a cellular receptor known as alpha-5-beta-1 integrin. The researchers examined these markers in hundreds of pancreatic tumors from patients treated at Fox Chase, using a new software and microscopy technique that allowed them to distinguish biomarker levels in cancer and stromal cells. They observed that the stromal biomarkers indicating a tumor-impeding environment were evident in patients that presented with longer recurrence-free survival than patients in which the tissue samples lacked these traits.
Results also suggested that stromal cells affected by pancreatic or renal cancers have the ability to produce a niche associated with shorter overall survival. Importantly, the team uncovered means to alter cells and their extracellular niches to switch tumor-promoting stroma into tumor-impeding stroma.
“More study is ongoing, but our work suggests the possibility of developing therapies that could modify tumor-promoting stroma to hinder a tumor’s growth,” Cukierman said.
The Chinese Society of Clinical Oncology honored Cukierman for this study with its Distinguished Achievement Award in Cancer Research and Clinical Management with a Focus on Pancreas.