Implantation of engineered adipocytes that outcompete tumors for resources suppresses cancer progression.


Journal

bioRxiv : the preprint server for biology
Titre abrégé: bioRxiv
Pays: United States
ID NLM: 101680187

Informations de publication

Date de publication:
29 Mar 2023
Historique:
pubmed: 11 4 2023
medline: 11 4 2023
entrez: 10 4 2023
Statut: epublish

Résumé

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.

Identifiants

pubmed: 37034710
doi: 10.1101/2023.03.28.534564
pmc: PMC10081280
pii:
doi:

Types de publication

Preprint

Langues

eng

Subventions

Organisme : NIDDK NIH HHS
ID : P30 DK098722
Pays : United States

Déclaration de conflit d'intérêts

Competing interests NA is a cofounder and on the scientific advisory board of Regel Therapeutics and Neomer Diagnostics. NA receives funding from BioMarin Pharmaceutical Incorporate. HPN and NA have filed a patent application covering embodiments and concepts disclosed in the manuscript.

Auteurs

Hai P Nguyen (HP)

Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.
Institute for Human Genetics, University of California San Francisco, San Francisco, CA, USA.

Rory Sheng (R)

Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.
Institute for Human Genetics, University of California San Francisco, San Francisco, CA, USA.

Elizabeth Murray (E)

Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.
Institute for Human Genetics, University of California San Francisco, San Francisco, CA, USA.

Yusuke Ito (Y)

Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.
Institute for Human Genetics, University of California San Francisco, San Francisco, CA, USA.

Michael Bruck (M)

Division of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.

Cassidy Biellak (C)

Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.
Institute for Human Genetics, University of California San Francisco, San Francisco, CA, USA.

Kelly An (K)

Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.
Institute for Human Genetics, University of California San Francisco, San Francisco, CA, USA.

Filipa Lynce (F)

Dana-Farber Cancer Institute, Harvard University, Boston, MA 02215, USA.

Deborah A Dillon (DA)

Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.

Mark Jesus M Magbanua (MJM)

Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 04158, USA.

Laura A Huppert (LA)

Division of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.

Heinz Hammerlindl (H)

Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.

Laura Esserman (L)

Department of Surgery, University of California, San Francisco, San Francisco, CA 94158, USA.

Jennifer M Rosenbluth (JM)

Division of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Chan Zuckerberg Biohub - San Francisco, San Francisco, CA 94158, USA.

Nadav Ahituv (N)

Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.
Institute for Human Genetics, University of California San Francisco, San Francisco, CA, USA.

Classifications MeSH