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Implantation of engineered adipocytes that outcompete tumors for resources suppresses cancer progression.
Nguyen, Hai P; Sheng, Rory; Murray, Elizabeth; Ito, Yusuke; Bruck, Michael; Biellak, Cassidy; An, Kelly; Lynce, Filipa; Dillon, Deborah A; Magbanua, Mark Jesus M; Huppert, Laura A; Hammerlindl, Heinz; Esserman, Laura; Rosenbluth, Jennifer M; Ahituv, Nadav.
Afiliación
  • Nguyen HP; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.
  • Sheng R; Institute for Human Genetics, University of California San Francisco, San Francisco, CA, USA.
  • Murray E; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.
  • Ito Y; Institute for Human Genetics, University of California San Francisco, San Francisco, CA, USA.
  • Bruck M; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.
  • Biellak C; Institute for Human Genetics, University of California San Francisco, San Francisco, CA, USA.
  • An K; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.
  • Lynce F; Institute for Human Genetics, University of California San Francisco, San Francisco, CA, USA.
  • Dillon DA; Division of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
  • Magbanua MJM; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.
  • Huppert LA; Institute for Human Genetics, University of California San Francisco, San Francisco, CA, USA.
  • Hammerlindl H; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.
  • Esserman L; Institute for Human Genetics, University of California San Francisco, San Francisco, CA, USA.
  • Rosenbluth JM; Dana-Farber Cancer Institute, Harvard University, Boston, MA 02215, USA.
  • Ahituv N; Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
bioRxiv ; 2023 Mar 29.
Article en En | MEDLINE | ID: mdl-37034710
Tumors acquire an increased ability to obtain and metabolize nutrients. Here, we engineered and implanted adipocytes to outcompete tumors for nutrients and show that they can substantially reduce cancer progression. Growing cells or xenografts from several cancers (breast, colon, pancreas, prostate) alongside engineered human adipocytes or adipose organoids significantly suppresses cancer progression and reduces hypoxia and angiogenesis. Transplanting modulated adipocyte organoids in pancreatic or breast cancer mouse models nearby or distal from the tumor significantly suppresses its growth. To further showcase therapeutic potential, we demonstrate that co-culturing tumor organoids derived from human breast cancers with engineered patient-derived adipocytes significantly reduces cancer growth. Combined, our results introduce a novel cancer therapeutic approach, termed adipose modulation transplantation (AMT), that can be utilized for a broad range of cancers.

Texto completo: 1 Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos