Implantation of engineered adipocytes suppresses tumor progression in cancer models.

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Tác giả: Nadav Ahituv, Kelly An, Daniel A Bernards, Cassandra Biellak, Michael Bruck, Tejal A Desai, Deborah A Dillon, Laura Esserman, Oliver Fiehn, Sarah L Fong, Heinz Hammerlindl, Laura A Huppert, Yusuke Ito, Bhushan N Kharbikar, Jace Anton Klein, Filipa Lynce, Mark Jesus M Magbanua, Elizabeth Murray, Hai P Nguyen, Mai Nobuhara, Breanna Paredes, Kimberly Pham, Jennifer M Rosenbluth, Rory Sheng, Aki Ushiki, Luis Valdiviez, Sook Wah Yee, Xujia Zhou

Ngôn ngữ: eng

Ký hiệu phân loại: 296.11643 Sources

Thông tin xuất bản: United States : Nature biotechnology , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 218281

Tumors exhibit an increased ability to obtain and metabolize nutrients. Here, we implant engineered adipocytes that outcompete tumors for nutrients and show that they can substantially reduce cancer progression, a technology termed adipose manipulation transplantation (AMT). Adipocytes engineered to use increased amounts of glucose and fatty acids by upregulating UCP1 were placed alongside cancer cells or xenografts, leading to significant cancer suppression. Transplanting modulated adipose organoids in pancreatic or breast cancer genetic mouse models suppressed their growth and decreased angiogenesis and hypoxia. Co-culturing patient-derived engineered adipocytes with tumor organoids from dissected human breast cancers significantly suppressed cancer progression and proliferation. In addition, cancer growth was impaired by inducing engineered adipose organoids to outcompete tumors using tetracycline or placing them in an integrated cell-scaffold delivery platform and implanting them next to the tumor. Finally, we show that upregulating UPP1 in adipose organoids can outcompete a uridine-dependent pancreatic ductal adenocarcinoma for uridine and suppress its growth, demonstrating the potential customization of AMT.
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