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

Nguyen, H. P.; Sheng, R.; Murray, E.; Ito, Y.; Bruck, M.; Biellak, C.; An, K.; Lynce, F.; Dillon, D. A.; Magbanua, M. J. M.; Huppert, L. A.; Hammerlindl, H.; Esserman, L.; Rosenbluth, J. M.; Ahituv, N.

doi:10.1101/2023.03.28.534564

bioRxiv · 10.1101/2023.03.28.534564

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

Nguyen, H. P.·Sheng, R.·Murray, E.·Ito, Y.·Bruck, M.·Biellak, C.·An, K.·Lynce, F.·Dillon, D. A.·Magbanua, M. J. M.·Huppert, L. A.·Hammerlindl, H.·Esserman, L.·Rosenbluth, J. M.·Ahituv, N.

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Abstract

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.

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Nguyen, H. P., Sheng, R., Murray, E., Ito, Y., Bruck, M., Biellak, C., An, K., Lynce, F., Dillon, D. A., Magbanua, M. J. M., Huppert, L. A., Hammerlindl, H., Esserman, L., Rosenbluth, J. M., Ahituv, N.. 2023-03-29. Implantation of engineered adipocytes that outcompete tumors for resources suppresses cancer progression. https://doi.org/10.1101/2023.03.28.534564

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