HomeDate: 2022-06-01
A research team led by Dr. Wen-Hwa Lee and Dr. Chun-Mei Hu from the Genomics Research Center revealed how PDAC tumor cells recruit nearby cells, called fibroblasts, to work as their helpers at tumor-stromal boundaries through direct tumor-fibroblast interaction. These interactions in PDAC progression enhance cancer cell migration and make the tumors more malignant. Blockage of direct contact between tumor cells and fibroblasts may represent a promising therapeutic strategy for patients with PDAC. This research was published in Nature Communications in May 2022.
Tumor cells with diverse phenotypes and biological behaviors are influenced by stromal cells through secretory factors or direct cell-cell contact. Pancreatic ductal adenocarcinoma (PDAC) is characterized by extensive desmoplasia with fibroblasts as the major cell type. The study observe enrichment of myofibroblasts in a juxta-tumoral position with tumor cells undergoing epithelial-mesenchymal transition (EMT) that facilitates invasion and correlates with a worse clinical prognosis in PDAC patients. Direct cell-cell contacts forming heterocellular aggregates between fibroblasts and tumor cells are detected in primary pancreatic tumors and circulating tumor microemboli (CTM). Mechanistically, ATP1A1 overexpressed in tumor cells binds to and reorganizes ATP1A1 of fibroblasts that induces calcium oscillations, NF-κB activation, and activin A secretion. Silencing ATP1A1 expression or neutralizing activin A secretion suppress tumor invasion and colonization. Taken together, these results elucidate the direct interplay between tumor cells and bound fibroblasts in PDAC progression, thereby providing potential therapeutic opportunities for inhibiting metastasis by interfering with these cell-cell interactions.
This research was completed by efforts from core team members, including Dr. Wen-Hwa Lee, Chun-Mei Hu, and Yi-Ing Chen. Appreciations to National Taiwan University physicians Dr. Yu-Wen Tien, Yu-Ting Chang, Ming-Chu Chang, and Yung-Ming Jeng. This study was published in Nature Communications on 26 May 2022.
