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Mitochondrial transfer from Adipose stem cells to breast cancer cells drives multi-drug resistance.
Del Vecchio, Vitale; Rehman, Ayesha; Panda, Sameer Kumar; Torsiello, Martina; Marigliano, Martina; Nicoletti, Maria Maddalena; Ferraro, Giuseppe Andrea; De Falco, Vincenzo; Lappano, Rosamaria; Lieto, Eva; Pagliuca, Francesca; Caputo, Carlo; La Noce, Marcella; Papaccio, Gianpaolo; Tirino, Virginia; Robinson, Nirmal; Desiderio, Vincenzo; Papaccio, Federica.
Afiliación
  • Del Vecchio V; Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Via L. Armanni, 5, 80138, Naples, Italy.
  • Rehman A; Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Via L. Armanni, 5, 80138, Naples, Italy.
  • Panda SK; Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Via L. Armanni, 5, 80138, Naples, Italy.
  • Torsiello M; Center for Cancer Biology, University of South Australia and SA Pathology, Adelaide, Australia.
  • Marigliano M; Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Via L. Armanni, 5, 80138, Naples, Italy.
  • Nicoletti MM; Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", Via Salvador Allende, 43, Baronissi, Sa, Italy.
  • Ferraro GA; Unit of Dermatology, Department of Mental, Physical and Preventive Medicine, University of Campania "Luigi Vanvitelli", Via L. De Crecchio, 6, 80138, Naples, Italy.
  • De Falco V; Plastic and Reconstructive Surgery Unit, Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania "Luigi Vanvitelli", Via L. De Crecchio, 6, 80138, Naples, Italy.
  • Lappano R; Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Via L. Armanni, 5, 80138, Naples, Italy.
  • Lieto E; Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Via Pietro Bucci, Arcavacata di Rende, 87036, CS, Italy.
  • Pagliuca F; Department of Translational Medicine, University of Campania "Luigi Vanvitelli" Via Leonardo Bianchi, 80131, Naples, Italy.
  • Caputo C; Department of Mental, Physical and Preventive Medicine, University of Campania "Luigi Vanvitelli", Largo Madonna delle Grazie n. 1, 80138, Naples, Italy.
  • La Noce M; Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Via De Crecchio, 7 - 80138, Naples, Italy.
  • Papaccio G; Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Via L. Armanni, 5, 80138, Naples, Italy.
  • Tirino V; Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Via L. Armanni, 5, 80138, Naples, Italy.
  • Robinson N; Unit of Cytometry and Mutational Diagnostics, AOU "Luigi Vanvitelli", Napoli, Italy.
  • Desiderio V; Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Via L. Armanni, 5, 80138, Naples, Italy.
  • Papaccio F; Unit of Cytometry and Mutational Diagnostics, AOU "Luigi Vanvitelli", Napoli, Italy.
J Exp Clin Cancer Res ; 43(1): 166, 2024 Jun 14.
Article en En | MEDLINE | ID: mdl-38877575
ABSTRACT

BACKGROUND:

Breast cancer (BC) is a complex disease, showing heterogeneity in the genetic background, molecular subtype, and treatment algorithm. Historically, treatment strategies have been directed towards cancer cells, but these are not the unique components of the tumor bulk, where a key role is played by the tumor microenvironment (TME), whose better understanding could be crucial to obtain better outcomes.

METHODS:

We evaluated mitochondrial transfer (MT) by co-culturing Adipose stem cells with different Breast cancer cells (BCCs), through MitoTracker assay, Mitoception, confocal and immunofluorescence analyses. MT inhibitors were used to confirm the MT by Tunneling Nano Tubes (TNTs). MT effect on multi-drug resistance (MDR) was assessed using Doxorubicin assay and ABC transporter evaluation. In addition, ATP production was measured by Oxygen Consumption rates (OCR) and Immunoblot analysis.

RESULTS:

We found that MT occurs via Tunneling Nano Tubes (TNTs) and can be blocked by actin polymerization inhibitors. Furthermore, in hybrid co-cultures between ASCs and patient-derived organoids we found a massive MT. Breast Cancer cells (BCCs) with ASCs derived mitochondria (ADM) showed a reduced HIF-1α expression in hypoxic conditions, with an increased ATP production driving ABC transporters-mediated multi-drug resistance (MDR), linked to oxidative phosphorylation metabolism rewiring.

CONCLUSIONS:

We provide a proof-of-concept of the occurrence of Mitochondrial Transfer (MT) from Adipose Stem Cells (ASCs) to BC models. Blocking MT from ASCs to BCCs could be a new effective therapeutic strategy for BC treatment.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Resistencia a Múltiples Medicamentos / Resistencia a Antineoplásicos / Mitocondrias Límite: Female / Humans Idioma: En Revista: J Exp Clin Cancer Res Año: 2024 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Resistencia a Múltiples Medicamentos / Resistencia a Antineoplásicos / Mitocondrias Límite: Female / Humans Idioma: En Revista: J Exp Clin Cancer Res Año: 2024 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Reino Unido