title: Human skin-derived fibroblasts acquire in vitro anti-tumor potential after priming with Paclitaxel.
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.
authors.affiliation: Department of Biomedical, Surgical and Dental Sciences, University of Milan, Via Pascal 36, 20133 Milan, Italy. augusto.pessina@unimi.it
authors.forename: Augusto
authors.initials: A
authors.lastname: Pessina
authors.forename: Valentina
authors.initials: V
authors.lastname: Coccè
authors.forename: Arianna
authors.initials: A
authors.lastname: Bonomi
authors.forename: Loredana
authors.initials: L
authors.lastname: Cavicchini
authors.forename: Francesca
authors.initials: F
authors.lastname: Sisto
authors.forename: Maura
authors.initials: M
authors.lastname: Ferrari
authors.forename: Emilio
authors.initials: E
authors.lastname: Ciusani
authors.forename: Stefania
authors.initials: S
authors.lastname: Navone
authors.forename: Giovanni
authors.initials: G
authors.lastname: Marfia
authors.forename: Eugenio
authors.initials: E
authors.lastname: Parati
authors.forename: Giulio
authors.initials: G
authors.lastname: Alessandri
mesh_terms: D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D001692:Biological Transport; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003692:Delayed-Action Preparations / Q000378:metabolism / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D017239:Paclitaxel / Q000378:metabolism / Q000494:pharmacology*; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D059016:Tumor Microenvironment
chemical_list: D000970:Antineoplastic Agents; D017077:Culture Media, Conditioned; D003692:Delayed-Action Preparations; D017239:Paclitaxel