Pancreatic stellate cells promote cancer cell proliferation, tumor growth

By Monish Makena, The Science Advisory Board contributing writer

January 25, 2022 -- Using optical imaging to study metabolic processes as they relate to tumor growth, researchers hope to better understand the tumor microenvironment and potential interventions. New research published on January 21 in Science Advances showed that pancreas cells co-cultured with pancreatic cancer cells in 3D organoids resulted in increased pancreatic cancer cell growth.

Pancreatic ductal adenocarcinoma (PDAC) is responsible for 7.3% of all cancer deaths. Even though there is a steady increase in patient survival for most cancers over the decades, the patient survival rate for pancreatic cancer remains low with current therapeutic strategies. The five-year survival rate for PDAC is 10%; in case of cancer metastasis, that rate lowers to 3%.

Pancreatic stellate cells (PSCs) are located in the exocrine regions of the pancreas and are reported to promote pancreatic cancer growth. In PDAC tumors, access to metabolic factors is very low. One hypothesis is that interactions with PSCs allow cancer cells to overcome this metabolic limitation of tumor growth.

In the current study, scientists at the Massachusetts Institute of Technology and the Morgridge Institute for Research in Madison, WI, used an optical redox imaging technique to investigate if PSCs can affect the metabolic state of pancreatic cancer cells.

The research team found that the optical redox ratio of PDAC cells was more oxidized in co-culture with PSCs than it was in monoculture, suggesting that PSCs can affect the redox state of PDAC cancer cells in co-culture conditions.

The authors also showed that co-culture with PSCs supports PDAC cell proliferation through the secretion of factors into the media, as well as by cell-cell interactions. These findings indicate that the PSCs in contact with cancer cells assume a more reduced redox state than those that are not in contact with cancer cells. Together, these data suggest that PSCs engage in a metabolic interaction with PDAC cells to promote a more oxidized state in cancer cells both in vitro and in vivo mouse models, which promotes tumor growth.

In conclusion, the research study highlights that the tumor microenvironment affects pancreatic tumor development and progression. Using a novel optical redox imaging, the authors demonstrated that the interaction of PSCs could help pancreatic cancer cells carry out oxidation reactions despite limited access to oxygen. This study provides novel insights into pancreatic cancer cell metabolism and tumor growth.

"I'm hoping this paper will show the power of our technique," Rupsa Datta, PhD, assistant scientist at the Morgridge Institute for Research, said in a statement. "Though, if more cancer labs adopted it, they would still need to collaborate with labs like ours with imaging expertise. But we love to collaborate!"

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