Journal Article

Adipose-derived stem cell-mediated paclitaxel delivery inhibits breast cancer growth

Scioli, Maria Giovanna, Artuso, Simona, Gentile, Pietro, Porru, Manuela, Leonetti, Carlo, D'Angelo, Carmen, Bielli, Alessandra, D’Amico, Federico, Orlandi, Augusto, Cervelli, Valerio

2018

Overview

Breast cancer represents the main malignancy in women and autologous fat grafting is a diffuse procedure in the management of post-surgical breast defects causing patients' psychosocial problems, with high costs for the public health. Recently, beneficial effects of fat grafting during post-surgical breast reconstruction have been amplified from the enrichment with human adipose-derived stem cells (ASCs) present in the stromal vascular fraction (SVF) of adult adipose tissue isolated during intraoperatory procedures. The major concern about the ASC enrichment during post-surgery breast reconstruction depends on their potential ability to release growth factors and hormones that can promote proliferation of residual or quiescent cancer cells, with the risk of de novo cancer development or recurrence. The recent description that adult stem cells primed in vitro may be vehicle for anti-cancer drug delivery offers a new vision concerning the role of ASCs in breast reconstruction after cancer surgery. Paclitaxel (PTX) is a chemotherapeutic agent acting as a microtubule-stabilizing drug inhibiting cancer cell mitotic activity. We optimized PTX loading and release in cultured ASCs and then analyzed the effects of PTX-loaded ASCs and their conditioned medium on CG5 breast cancer survival, proliferation and apoptosis in vitro, and inCG5 xenograft in vivo. We documented that ASCs can uptake and release PTX in vitro, with slight cytotoxic effects. Interestingly, PTX-loaded ASCs in co-culture, as well as conditioned medium alone, inhibited CG5 cell proliferation and survival in vitro and xenograft tumor growth in vivo. The antitumor effect of PTX-loaded ASCs may offer a new perspective concerning the use of ASCs during breast reconstruction becoming an additional local preventive chemotherapeutic agent against tumor recurrence. However, further experiments in vitro and in vivo are needed to collect more evidence confirming the efficacy and safety in cancer patients.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adipocytes / Adipose tissue / Adipose Tissue - cytology / Animals / Anticancer properties / Antineoplastic Agents, Phytogenic - administration & dosage / Antineoplastic Agents, Phytogenic - pharmacokinetics / Antineoplastic Agents, Phytogenic - pharmacology / Antitumor activity / Apoptosis / Apoptosis - drug effects / Autografts / Biology and Life Sciences / Breast cancer / Breast Neoplasms - drug therapy / Breast Neoplasms - pathology / Cancer / Cancer therapies / Cell culture / Cell growth / Cell proliferation / Cell Proliferation - drug effects / Cell survival / Cells, Cultured / Conditioning / Culture Media, Conditioned - pharmacology / Cytotoxicity / Development and progression / Dosage and administration / Drug delivery / Drug delivery systems / Drug therapy / Enrichment / Female / Grafting / Growth factors / Health aspects / Health risks / Hormones / Humans / Malignancy / MCF-7 Cells / Medicine and Health Sciences / Mice, Nude / Paclitaxel / Paclitaxel - administration & dosage / Paclitaxel - pharmacokinetics / Paclitaxel - pharmacology / Pathology / Patients / Plastic surgery / Prevention / Public health / Reagents / Reconstruction / Stem cells / Stem Cells - metabolism / Studies / Surgery / Survival / Tumor Burden - drug effects / Tumors / Xenograft Model Antitumor Assays / Xenografts / Xenotransplantation