Human Skin-Derived Fibroblasts Acquire In Vitro Anti-Tumor Potential after Priming with Paclitaxel

Title:Human Skin-Derived Fibroblasts Acquire In Vitro Anti-Tumor Potential after Priming with Paclitaxel

Volume: 13 Issue: 3

Author(s): Augusto Pessina, Valentina Cocce, Arianna Bonomi, Loredana Cavicchini, Francesca Sisto, Maura Ferrari, Emilio Ciusani, Stefania Navone, Giovanni Marfia, Eugenio Parati and Giulio Alessandri

Affiliation:

Keywords: Drug uptake, Mesenchymal stem cells, Skin dermal fibroblasts, Stromal cells, Taxol

Abstract: The main goal in cancer chemotherapy is to drive the drug into the tumor microenvironment to kill as many cancer cells as possible while producing the lowest collateral toxicity. Previously, we have shown that human bone marrow derived mesenchymal stromal cells (hBM-MSCs) exposed to Paclitaxel (PTX) were able to uptake and subsequently release the drug in the culture medium. PTX primed hBM-MSCs (hBM-MSCsPTX) located in the vicinity of cancer cells produced a strong inhibition of tumor cell growth both in vitro and in vivo. To expand these observations, in the present study we exposed human skin derived fibroblasts (hSDFs) to 2,000 ng/ml of PTX and then tested both cells and their conditioned medium (CM) in vitro for their capacity to inhibit the proliferation of human tumor cell lines (MOLT-4, DU-145, U87-MG, SH-SY5Y(+) and LAN-5). We found that hSDFs primed with PTX (hSDFsPTX) were able to uptake and subsequently release PTX in a time dependent manner. hSDFsPTX-derived CM(hSDFsPTX-CM) from 1:4 to 1:10 dilutions produced a significant (p<0.05) in vitro tumor growth inhibition. hSDFsPTX co-cultured with leukemia cells at 1:1 to 1:10 ratio, completely inhibited cells growth whereas no inhibition was induced by normal hSDFs cells. Our results demonstrate for the first time that hSDFs can be loaded in vitro with PTX and thus can acquire a potent anti-tumor activity. Since hSDFs can be easily isolated from skin biopsies without any particular pain and discomfort to donor patients, we conclude that hSDFs may represent a valid cell type option for carrying and delivering anti-cancer drugs.

Cite this article as:

Pessina Augusto, Cocce Valentina, Bonomi Arianna, Cavicchini Loredana, Sisto Francesca, Ferrari Maura, Ciusani Emilio, Navone Stefania, Marfia Giovanni, Parati Eugenio and Alessandri Giulio, Human Skin-Derived Fibroblasts Acquire In Vitro Anti-Tumor Potential after Priming with Paclitaxel, Anti-Cancer Agents in Medicinal Chemistry 2013; 13 (3) . https://dx.doi.org/10.2174/1871520611313030015