PMID- 31137684
OWN - NLM
STAT- MEDLINE
DCOM- 20200106
LR  - 20200309
IS  - 2073-4409 (Print)
IS  - 2073-4409 (Electronic)
IS  - 2073-4409 (Linking)
VI  - 8
IP  - 5
DP  - 2019 May 24
TI  - TNF-alpha Modulates P-Glycoprotein Expression and Contributes to Cellular 
      Proliferation via Extracellular Vesicles.
LID - 10.3390/cells8050500 [doi]
LID - 500
AB  - P-glycoprotein (Pgp/ABCB1) overexpression is associated with multidrug resistance 
      (MDR) phenotype and, consequently, failure in cancer chemotherapy. However, 
      molecules involved in cell death deregulation may also support MDR. Tumor 
      necrosis factor-alpha (TNF-alpha) is an important cytokine that may trigger either 
      death or tumor growth. Here, we examined the role of cancer cells in 
      self-maintenance and promotion of cellular malignancy through the transport of 
      Pgp and TNF-alpha molecules by extracellular vesicles (membrane microparticles (MP)). 
      By using a classical MDR model in vitro, we identified a positive correlation 
      between endogenous TNF-alpha and Pgp, which possibly favored a non-cytotoxic effect 
      of recombinant TNF-alpha (rTNF-alpha). We also found a positive feedback involving rTNF-alpha 
      incubation and TNF-alpha regulation. On the other hand, rTNF-alpha induced a reduction in 
      Pgp expression levels and contributed to a reduced Pgp efflux function. Our 
      results also showed that parental and MDR cells spontaneously released MP 
      containing endogenous TNF-alpha and Pgp. However, these MP were unable to transfer 
      their content to non-cancer recipient cells. Nevertheless, MP released from 
      parental and MDR cells elevated the proliferation index of non-tumor cells. 
      Collectively, our results suggest that Pgp and endogenous TNF-alpha positively 
      regulate cancer cell malignancy and contribute to changes in normal cell behavior 
      through MP.
FAU - Berguetti, Tandressa
AU  - Berguetti T
AD  - Laboratorio de Hemato-Oncologia Celular e Molecular, Programa de Hemato-Oncologia 
      Molecular, Instituto Nacional de Cancer (INCA), Rio de Janeiro 20231-050, Brazil. 
      tata.berguetti@hotmail.com.
AD  - Programa de Pos-Graduacao Strictu Sensu em Oncologia, INCA, Rio de Janeiro 
      20231-050, Brazil. tata.berguetti@hotmail.com.
FAU - Quintaes, Lucas S P
AU  - Quintaes LSP
AD  - Laboratorio de Hemato-Oncologia Celular e Molecular, Programa de Hemato-Oncologia 
      Molecular, Instituto Nacional de Cancer (INCA), Rio de Janeiro 20231-050, Brazil. 
      lucas.s.p.quintaes@gmail.com.
FAU - Hancio, Thais
AU  - Hancio T
AD  - Laboratorio de Hemato-Oncologia Celular e Molecular, Programa de Hemato-Oncologia 
      Molecular, Instituto Nacional de Cancer (INCA), Rio de Janeiro 20231-050, Brazil. 
      thais.hancio@gmail.com.
AD  - Programa de Pos-Graduacao Strictu Sensu em Oncologia, INCA, Rio de Janeiro 
      20231-050, Brazil. thais.hancio@gmail.com.
FAU - Robaina, Marcela C
AU  - Robaina MC
AUID- ORCID: 0000-0002-0705-7507
AD  - Laboratorio de Hemato-Oncologia Celular e Molecular, Programa de Hemato-Oncologia 
      Molecular, Instituto Nacional de Cancer (INCA), Rio de Janeiro 20231-050, Brazil. 
      mrobaina@ymail.com.
FAU - Cruz, Andre L S
AU  - Cruz ALS
AD  - Laboratorio de Fisiopatologia, Polo Novo Cavaleiros, Campus UFRJ-Macae, 
      Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-909, Brazil. 
      andrecruz@macae.ufrj.br.
FAU - Maia, Raquel C
AU  - Maia RC
AD  - Laboratorio de Hemato-Oncologia Celular e Molecular, Programa de Hemato-Oncologia 
      Molecular, Instituto Nacional de Cancer (INCA), Rio de Janeiro 20231-050, Brazil. 
      rcmaia@inca.gov.br.
FAU - de Souza, Paloma Silva
AU  - de Souza PS
AD  - Laboratorio de Hemato-Oncologia Celular e Molecular, Programa de Hemato-Oncologia 
      Molecular, Instituto Nacional de Cancer (INCA), Rio de Janeiro 20231-050, Brazil. 
      paloma.inca@gmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190524
PL  - Switzerland
TA  - Cells
JT  - Cells
JID - 101600052
RN  - 0 (ABCB1 protein, human)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Recombinant Proteins)
RN  - 0 (TNF protein, human)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily B/metabolism
MH  - Antineoplastic Agents/pharmacology
MH  - Apoptosis/drug effects
MH  - *Cell Proliferation
MH  - Cell Survival/drug effects
MH  - Drug Resistance, Multiple/drug effects
MH  - Drug Resistance, Neoplasm/drug effects
MH  - Extracellular Vesicles/*metabolism
MH  - Feedback, Physiological
MH  - Fibroblasts/metabolism
MH  - Humans
MH  - KB Cells
MH  - Neoplasms/*metabolism/pathology
MH  - Protein Transport
MH  - Recombinant Proteins/pharmacology
MH  - Tumor Necrosis Factor-alpha/genetics/*metabolism
PMC - PMC6562596
OTO - NOTNLM
OT  - ABCB1
OT  - MDR
OT  - P-glycoprotein
OT  - TNF-alpha
OT  - drug resistance
OT  - extracellular vesicles
OT  - microparticles
COIS- The authors declare no conflict of interest.
EDAT- 2019/05/30 06:00
MHDA- 2019/05/30 06:01
PMCR- 2019/05/01
CRDT- 2019/05/30 06:00
PHST- 2019/03/26 00:00 [received]
PHST- 2019/05/21 00:00 [revised]
PHST- 2019/05/23 00:00 [accepted]
PHST- 2019/05/30 06:00 [entrez]
PHST- 2019/05/30 06:00 [pubmed]
PHST- 2019/05/30 06:01 [medline]
PHST- 2019/05/01 00:00 [pmc-release]
AID - cells8050500 [pii]
AID - cells-08-00500 [pii]
AID - 10.3390/cells8050500 [doi]
PST - epublish
SO  - Cells. 2019 May 24;8(5):500. doi: 10.3390/cells8050500.