PMID- 36046354
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220907
IS  - 2692-3114 (Electronic)
IS  - 2692-3114 (Linking)
VI  - 3
IP  - 1
DP  - 2022
TI  - Bcl-2-like protein-10 increases aggressive features of melanoma cells.
PG  - 11-26
LID - 10.37349/etat.2022.00068 [doi]
AB  - AIM: B-cell lymphoma-2 (Bcl-2)-like protein-10 (Bcl2L10) is the less studied 
      member of Bcl-2 family proteins, with the controversial role in different cancer 
      histotypes. Very recently, Bcl2L10 expression in melanoma tumor specimens and its 
      role in melanoma response to therapy have been demonstrated. Here, the 
      involvement of Bcl2L10 on the in vitro and in vivo properties associated with 
      melanoma aggressive features has been investigated. METHODS: Endogenous Bcl2L10 
      protein expression was detected by western blotting analysis in a panel of 
      patient-derived and commercially available human melanoma cells. In vitro assays 
      to evaluate clonogenicity, cell proliferation, cell migration, cell invasion, and 
      in vitro capillary-like structure formation [vasculogenic mimicry (VM)] have been 
      performed by using human melanoma cells stably overexpressing Bcl2L10 or 
      transiently transfected for loss/gain function of Bcl2L10, grown under two- or 
      three-dimensional (3D) conditions Xenograft melanoma model was employed to 
      evaluate in vivo tumor growth and angiogenesis. RESULTS: Results demonstrated 
      that Bcl2L10 acts as an inducer of in vitro cell migration, invasion, and VM, 
      while in vitro cell proliferation, in vivo tumor growth, as well as colony 
      formation properties were not affected. Dissecting different signaling pathways, 
      it was found that Bcl2L10 positively affects the phosphorylation of 
      extracellular-signal-regulated kinase (ERK) and the expression of markers of cell 
      invasion, such as urokinase plasminogen activator receptor (uPAR) and matrix 
      metalloproteinases (MMPs). Of note, Bcl2L10-dependent in vitro migration, 
      invasion, and VM are linked to uPAR. Bcl2L10 also negatively regulates the 
      intracellular calcium level. Finally, reduced invasion capability in 3D spheroid 
      invasion assay of melanoma cells transiently overexpressing Bcl2L10 was observed 
      after treatment with inhibitors of MMPs and uPAR. CONCLUSIONS: Overall, data 
      reported in this paper provide evidence supporting a positive role of Bcl2L10 in 
      melanoma aggressive features.
CI  - (c) The Author(s) 2022.
FAU - Del Bufalo, Donatella
AU  - Del Bufalo D
AUID- ORCID: 0000-0002-3148-6096
AD  - Preclinical Models and New Therapeutic Agents Unit, IRCCS Regina Elena National 
      Cancer Institute, 00144 Rome, Italy.
FAU - Di Martile, Marta
AU  - Di Martile M
AUID- ORCID: 0000-0001-9924-9022
AD  - Preclinical Models and New Therapeutic Agents Unit, IRCCS Regina Elena National 
      Cancer Institute, 00144 Rome, Italy.
FAU - Valentini, Elisabetta
AU  - Valentini E
AUID- ORCID: 0000-0003-3073-3590
AD  - Preclinical Models and New Therapeutic Agents Unit, IRCCS Regina Elena National 
      Cancer Institute, 00144 Rome, Italy.
FAU - Manni, Isabella
AU  - Manni I
AUID- ORCID: 0000-0003-4823-0596
AD  - SAFU Unit, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy.
FAU - Masi, Ilenia
AU  - Masi I
AD  - Institute of Molecular Biology and Pathology, National Research Council, 00161 
      Rome, Italy.
FAU - D'Amore, Antonella
AU  - D'Amore A
AUID- ORCID: 0000-0002-3441-4397
AD  - Unit of Histology and Medical Embryology, Department of Anatomy, Histology, 
      Forensic Medicine and Orthopaedics, Sapienza University, 00161 Rome, Italy.
FAU - Filippini, Antonio
AU  - Filippini A
AUID- ORCID: 0000-0001-8453-287X
AD  - Unit of Histology and Medical Embryology, Department of Anatomy, Histology, 
      Forensic Medicine and Orthopaedics, Sapienza University, 00161 Rome, Italy.
FAU - Nicoletti, Carmine
AU  - Nicoletti C
AUID- ORCID: 0000-0001-5896-2040
AD  - Unit of Histology and Medical Embryology, Department of Anatomy, Histology, 
      Forensic Medicine and Orthopaedics, Sapienza University, 00161 Rome, Italy.
FAU - Zaccarini, Marco
AU  - Zaccarini M
AUID- ORCID: 0000-0001-6903-3343
AD  - Genetic Research, Dermatological Molecular Biology and Dermatopathology Unit, 
      IRCCS San Gallicano Dermatological Institute, 00144 Rome, Italy.
FAU - Cota, Carlo
AU  - Cota C
AUID- ORCID: 0000-0001-6335-8649
AD  - Genetic Research, Dermatological Molecular Biology and Dermatopathology Unit, 
      IRCCS San Gallicano Dermatological Institute, 00144 Rome, Italy.
FAU - Castro, Maria Victoria
AU  - Castro MV
AD  - Centro de Estudios Biomedicos, Basicos, Aplicados y Desarrollo, Universidad 
      Maimonides, Buenos Aires C1405BCK, Argentina.
AD  - Consejo Nacional de Investigaciones Cientificas y Tecnicas, Buenos Aires 
      C1405BCK, Argentina.
FAU - Quezada, Maria Josefina
AU  - Quezada MJ
AUID- ORCID: 0000-0002-9676-1124
AD  - Centro de Estudios Biomedicos, Basicos, Aplicados y Desarrollo, Universidad 
      Maimonides, Buenos Aires C1405BCK, Argentina.
AD  - Consejo Nacional de Investigaciones Cientificas y Tecnicas, Buenos Aires 
      C1405BCK, Argentina.
FAU - Rosano, Laura
AU  - Rosano L
AUID- ORCID: 0000-0002-3981-8593
AD  - Preclinical Models and New Therapeutic Agents Unit, IRCCS Regina Elena National 
      Cancer Institute, 00144 Rome, Italy.
AD  - Institute of Molecular Biology and Pathology, National Research Council, 00161 
      Rome, Italy.
FAU - Lopez-Bergami, Pablo
AU  - Lopez-Bergami P
AUID- ORCID: 0000-0001-8669-6931
AD  - Centro de Estudios Biomedicos, Basicos, Aplicados y Desarrollo, Universidad 
      Maimonides, Buenos Aires C1405BCK, Argentina.
AD  - Consejo Nacional de Investigaciones Cientificas y Tecnicas, Buenos Aires 
      C1405BCK, Argentina.
FAU - D'Aguanno, Simona
AU  - D'Aguanno S
AUID- ORCID: 0000-0002-1224-4454
AD  - Preclinical Models and New Therapeutic Agents Unit, IRCCS Regina Elena National 
      Cancer Institute, 00144 Rome, Italy.
LA  - eng
PT  - Journal Article
DEP - 20220130
PL  - United States
TA  - Explor Target Antitumor Ther
JT  - Exploration of targeted anti-tumor therapy
JID - 101770662
PMC - PMC9400776
OTO - NOTNLM
OT  - B-cell lymphoma-2-like protein-10
OT  - invasion
OT  - melanoma
OT  - migration
OT  - vasculogenic mimicry
COIS- The authors declare that there are no conflicts of interest.
EDAT- 2022/09/02 06:00
MHDA- 2022/09/02 06:01
PMCR- 2022/01/30
CRDT- 2022/09/01 02:27
PHST- 2021/09/20 00:00 [received]
PHST- 2021/12/20 00:00 [accepted]
PHST- 2022/09/02 06:00 [pubmed]
PHST- 2022/09/02 06:01 [medline]
PHST- 2022/09/01 02:27 [entrez]
PHST- 2022/01/30 00:00 [pmc-release]
AID - etat-03-100268 [pii]
AID - 10.37349/etat.2022.00068 [doi]
PST - ppublish
SO  - Explor Target Antitumor Ther. 2022;3(1):11-26. doi: 10.37349/etat.2022.00068. 
      Epub 2022 Jan 30.