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Open AccessArticle

Targeting Melanoma Hypoxia with the Food-Grade Lactic Acid Bacterium Lactococcus Lactis

1
Department of Surgery, School of Medicine, University of Louisville, Louisville, KY 40202, USA
2
Molecular Targets Program, James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA
3
Department of Microbiology, School of Medicine, University of Louisville, Louisville, KY 40202, USA
4
INRAE, AgroParisTech, Micalis Institute, Université Paris-Saclay, 78350 Jouy-en-Josas, France
5
Department of Bioengineering, Stephenson Cancer Center, University of Oklahoma, Norman, OK 73019, USA
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(2), 438; https://doi.org/10.3390/cancers12020438
Received: 27 December 2019 / Revised: 7 February 2020 / Accepted: 10 February 2020 / Published: 13 February 2020
(This article belongs to the Special Issue Targeting Solid Tumors)
Melanoma is the most aggressive form of skin cancer. Hypoxia is a feature of the tumor microenvironment that reduces efficacy of immuno- and chemotherapies, resulting in poor clinical outcomes. Lactococcus lactis is a facultative anaerobic gram-positive lactic acid bacterium (LAB) that is Generally Recognized as Safe (GRAS). Recently, the use of LAB as a delivery vehicle has emerged as an alternative strategy to deliver therapeutic molecules; therefore, we investigated whether L. lactis can target and localize within melanoma hypoxic niches. To simulate hypoxic conditions in vitro, melanoma cells A2058, A375 and MeWo were cultured in a chamber with a gas mixture of 5% CO2, 94% N2 and 1% O2. Among the cell lines tested, MeWo cells displayed greater survival rates when compared to A2058 and A375 cells. Co-cultures of L. lactis expressing GFP or mCherry and MeWo cells revealed that L. lactis efficiently express the transgenes under hypoxic conditions. Moreover, multispectral optoacoustic tomography (MSOT), and near infrared (NIR) imaging of tumor-bearing BALB/c mice revealed that the intravenous injection of either L. lactis expressing β-galactosidase (β-gal) or infrared fluorescent protein (IRFP713) results in the establishment of the recombinant bacteria within tumor hypoxic niches. Overall, our data suggest that L. lactis represents an alternative strategy to target and deliver therapeutic molecules into the tumor hypoxic microenvironment. View Full-Text
Keywords: Lactococcus lactis; probiotic; hypoxia; melanoma; tumor microenvironment; MSOT; advance molecular imaging (AMI), targeted therapies; solid tumors Lactococcus lactis; probiotic; hypoxia; melanoma; tumor microenvironment; MSOT; advance molecular imaging (AMI), targeted therapies; solid tumors
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MDPI and ACS Style

Garza-Morales, R.; Rendon, B.E.; Malik, M.T.; Garza-Cabrales, J.E.; Aucouturier, A.; Bermúdez-Humarán, L.G.; McMasters, K.M.; McNally, L.R.; Gomez-Gutierrez, J.G. Targeting Melanoma Hypoxia with the Food-Grade Lactic Acid Bacterium Lactococcus Lactis. Cancers 2020, 12, 438. https://doi.org/10.3390/cancers12020438

AMA Style

Garza-Morales R, Rendon BE, Malik MT, Garza-Cabrales JE, Aucouturier A, Bermúdez-Humarán LG, McMasters KM, McNally LR, Gomez-Gutierrez JG. Targeting Melanoma Hypoxia with the Food-Grade Lactic Acid Bacterium Lactococcus Lactis. Cancers. 2020; 12(2):438. https://doi.org/10.3390/cancers12020438

Chicago/Turabian Style

Garza-Morales, Rodolfo; Rendon, Beatriz E.; Malik, Mohammad T.; Garza-Cabrales, Jeannete E.; Aucouturier, Anne; Bermúdez-Humarán, Luis G.; McMasters, Kelly M.; McNally, Lacey R.; Gomez-Gutierrez, Jorge G. 2020. "Targeting Melanoma Hypoxia with the Food-Grade Lactic Acid Bacterium Lactococcus Lactis" Cancers 12, no. 2: 438. https://doi.org/10.3390/cancers12020438

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