Implantation of engineered adipocytes that outcompete tumors for resources suppresses cancer progression
Tumors acquire an increased ability to obtain and metabolize nutrients. Here, we engineered adipocytes to outcompete tumors for nutrients and show that they can substantially reduce cancer progression. Growing cells from several cancers (breast, colon, pancreas, prostate) with engineered human adipocytes or xenografts alongside adipose organoids significantly suppresses cancer progression and reduces hypoxia and angiogenesis. Transplanting modulated adipocyte organoids in pancreatic or breast cancer genetic mouse models significantly suppressed their growth and decreased angiogenesis and hypoxia. To further showcase therapeutic potential, we demonstrate that co-culturing engineered patient-derived adipocytes with tumor organoids from dissected human breast cancers significantly reduces cancer growth and reduces proliferation of organoids from donors with BRCA1/2 mutations. In addition, inducing adipose organoids to outcompete tumors via tetracycline or placing them in an integrated cell-scaffold delivery platform and implanting them next to the tumor, both significantly suppress cancer growth. Finally, to display how this approach can be customized for different tumor-associated metabolic programs, we show that upregulating UPP1 in adipose organoids can outcompete a uridine-dependent pancreatic ductal adenocarcinoma for resources and suppress its 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. Overall design: RNA samples isolated MCF7 xenograft tumors that were co-implanted with either UCP1-CRISRPa modualted-  or dCas9-VP64 (control) treated- adipose organoids in SCID micce fed with chow, high-fet diet, or 15% glucose water